Liposome is one of the most widely used carriers for drug delivery because of the great biocompatibility and biodegradability.Due to the complex formulation components and preparation process,formulation screening mos...Liposome is one of the most widely used carriers for drug delivery because of the great biocompatibility and biodegradability.Due to the complex formulation components and preparation process,formulation screening mostly relies on trial-and-error process with low efficiency.Here liposome formulation prediction models have been built by machine learning(ML)approaches.The important parameters of liposomes,including size,polydispersity index(PDI),zeta potential and encapsulation,are predicted individually by optimal ML algorithm,while the formulation features are also ranked to provide important guidance for formulation design.The analysis of key parameter reveals that drug molecules with logS[-3,-6],molecular complexity[500,1000]and XLogP3(≥2)are priority for preparing liposome with higher encapsulation.In addition,naproxen(NAP)and palmatine HCl(PAL)represented the insoluble and water-soluble molecules are prepared as liposome formulations to validate prediction ability.The consistency between predicted and experimental value verifies the satisfied accuracy of ML models.As the drug properties are critical for liposome particles,the molecular interactions and dynamics of NAP and PAL liposome are further investigated by coarse-grained molecular dynamics simulations.The modeling structure reveals that NAP molecules could distribute into lipid layer,while most PAL molecules aggregate in the inner aqueous phase of liposome.The completely different physical state of NAP and PAL confirms the importance of drug properties for liposome formulations.In summary,the general prediction models are built to predict liposome formulations,and the impacts of key factors are analyzed by combing ML with molecular modeling.The availability and rationality of these intelligent prediction systems have been proved in this study,which could be applied for liposome formulation development in the future.展开更多
Although vaccines have been developed,mutations of SARS-CoV-2,especially the dominant B.1.617.2(delta)and B.1.529(omicron)strains with more than 30 mutations on their spike protein,have caused a significant decline in...Although vaccines have been developed,mutations of SARS-CoV-2,especially the dominant B.1.617.2(delta)and B.1.529(omicron)strains with more than 30 mutations on their spike protein,have caused a significant decline in prophylaxis,calling for the need for drug improvement.Antibodies are drugs preferentially used in infectious diseases and are easy to get from immunized organisms.The current study combined molecular modeling and single memory B cell sequencing to assess candidate sequences before experiments,providing a strategy for the fabrication of SARS-CoV-2 neutralizing antibodies.A total of 128 sequences were obtained after sequencing 196 memory B cells,and 42 sequences were left after merging extremely similar ones and discarding incomplete ones,followed by homology modeling of the antibody variable region.Thirteen candidate sequences were expressed,of which three were tested positive for receptor binding domain recognition but only one was confirmed as having broad neutralization against several SARS-CoV-2 variants.The current study successfully obtained a SARS-CoV-2 antibody with broad neutralizing abilities and provided a strategy for antibody development in emerging infectious diseases using single memory B cell BCR sequencing and computer assistance in antibody fabrication.展开更多
A novel ligand N-4-hydroxyacetophenone isonicotinoyl hydrazone and its manganese(II) and nickel(II) metal complexes have been synthesized. The synthesized Schiff base and its metal complexes have been characterized by...A novel ligand N-4-hydroxyacetophenone isonicotinoyl hydrazone and its manganese(II) and nickel(II) metal complexes have been synthesized. The synthesized Schiff base and its metal complexes have been characterized by physical state determination, melting point and solubility measurements in different solvents, infrared, proton nuclear magnetic resonance, mass spectrometric and powder X-ray spectroscopic techniques. The thermal properties of the prepared compounds were obtained from TG/DTG measurements. On the basis of the analytical techniques, the ligand was found to be bidentate in nature coordinating to the metal ions through the azomethine nitrogen and carbonyl oxygen atoms leading to distorted octahedral geometries of the metal complexes which were modeled using MM2 force field. The ligand and its metal(II) complexes were evaluated for antifungal activity against <i>Aspergillus fumigatus, Aspergillus niger, Candida albicans and Rhizopus stolonifera.</i> The antifungal evaluation results revealed an enhanced activity upon coordination of the ligand with the metal(II) ions. The activity of the metal complex to the tested fungal strains was in the order Ni(II) > Mn(II).展开更多
An insight into the interaction of collagen type I with apatite in bone tissue was performed by using differential scanning calorimetry, Fourier transform infrared spectroscopy, and molecular modeling. Scanning electr...An insight into the interaction of collagen type I with apatite in bone tissue was performed by using differential scanning calorimetry, Fourier transform infrared spectroscopy, and molecular modeling. Scanning electron microscopy shows that bone organic content incinerate gradually through the different temperatures studied. We suggest that the amide regions of the type I collagen molecule (mainly C=O groups of the peptide bonds) will be important in the control of the interactions with the apatite from bone. The amide I infrared bands of the collagen type I change when interacting to apatite, what might confirm our assumption. Bone tissue results in a loss of thermal stability compared to the collagen studied apart, as a consequence of the degradation and further combustion of the collagen in contact with the apatite microcrystals in bone. The thermal behavior of bone is very distinctive. Its main typical combustion temperature is at 360°C with a shoulder at 550°C compared to the thermal behavior of collagen, with the mean combustion peak at ca. 500°C. Our studies with molecular mechanics (MM+ force field) showed different interaction energies of the collagen-like molecule and different models of the apatite crystal planes. We used models of the apatite (100) and (001) planes;additional two planes (001) were explored with phosphate-rich and calcium-rich faces;an energetic preference was found in the latter case. We preliminary conclude that the peptide bond of collagen type I is modified when the molecule interacts with the apatite, producing a decrease in the main peak from ca. 500°C in collagen, up to 350°C in bone. The combustion might be related to collagen type I, as the ΔH energies present only small variations between mineralized and non-mineralized samples. The data obtained here give a molecular perspective into the structural properties of bone and the change in collagen properties caused by the interaction with the apatite. Our study can be useful to understand the biological synthesis of minerals as well as the organic-inorganic interaction and the synthesis of apatite implant materials.展开更多
Carbamates are molecules that have different types of biological activities and provide a particular chemical control against ticks. The new structures of the proposed compounds were optimized and synthetized respecti...Carbamates are molecules that have different types of biological activities and provide a particular chemical control against ticks. The new structures of the proposed compounds were optimized and synthetized respectively, through a molecular model using the methods:PM3, HF and DFT applying the B3LYP functional, with the basis 6-31+G(d) and 6-311+G(d,p), BVP86 and PBEPBE with 6-31+G(d) and the vibrational frequencies computed. These calculated frequencies were compared with the experimental ones to determine the most accurate level of theory for the prediction of vibrational frequencies of the compounds. The best results were obtained through HF/631+G(d). Additionally, we report a modification to obtain this type of compounds, and based on the amino-dehalogenation of ethyl chloroformate, different benzyl ethyl carbamates were synthesized modifying the base molecule. The performances obtained were compared to others already reported. The methodology used allowed us to synthesize new carbamates using benzylamine derivatives through a modification on the basic catalysis of the addition-elimination reaction.展开更多
Aggregation of amyloid ?-peptide (A?) into insoluble fibrils is a key pathological event in Alzheimer’s disease (AD). Under certain conditions, Cu(II) exhibits strong inhibitory ef-fect on the Zn(II)-induced aggregat...Aggregation of amyloid ?-peptide (A?) into insoluble fibrils is a key pathological event in Alzheimer’s disease (AD). Under certain conditions, Cu(II) exhibits strong inhibitory ef-fect on the Zn(II)-induced aggregation, which occurs significantly even at nearly physiological concentrations of zinc ion in vitro. Cu(II) is considered as a potential factor in the normal brain preventing A? from aggregating. The possible mechanism of the inhibitory effect of Cu(II) is in-vestigated for the first time by molecular modeling method. In the mono-ring mode, the Y10 residue promotes typical quasi-helix conformations of A?. Specially, [Cu-H13(Np)-Y10(OH)] complex forms a local 3.010 helix conformation. In the multi-ring mode, the side chains of Q15 and E11 residues collaborate harmoniously with other chelating ligands producing markedly low energies and quasi-helix conformations. [Cu-3N-Q15(O)-E11(O1)] and [Cu-H13(Np)-Y10(OH)] complex with quasi-helix conformations may prefer soluble forms in solution. In addition, hydro-gen-bond interactions may be the main driving force for A? aggregation. All the results will pro-vide helpful clues for an improved understanding of the role of Cu(II) in the pathogenesis of AD and contribute to the development of an “anti-amyloid” therapeutic strategy.展开更多
APOBEC3G(A3G)is a host cytidine deaminase that incorporates into HIV-1 virions and efficiently inhibits viral replication.The virally encoded protein Vif binds to A3G and induces its degradation,thereby counteracting ...APOBEC3G(A3G)is a host cytidine deaminase that incorporates into HIV-1 virions and efficiently inhibits viral replication.The virally encoded protein Vif binds to A3G and induces its degradation,thereby counteracting the antiviral activity of A3G.Vif-mediated A3G degradation clearly represents a potential target for anti-HIV drug development.Currently,there is an urgent need for understanding the three dimensional structure of full-length A3G.In this work,we use a homology modeling approach to propose a structure for A3G based on the crystal structure of APOBEC2(APO2)and the catalytic domain structure of A3G.Two compounds,IMB26 and IMB35,which have been shown to bind to A3G and block degradation by Vif,were docked into the A3G model and the binding modes were generated for further analysis.The results may be used to design or optimize molecules targeting Vif–A3G interaction,and lead to the development of novel anti-HIV drugs.展开更多
Crystal structure of conjugated molecules and polymers is fundamentally critical to understand their multilevel microstructures,carrier transport,and diverse functions.However,to determine the crystal structure of con...Crystal structure of conjugated molecules and polymers is fundamentally critical to understand their multilevel microstructures,carrier transport,and diverse functions.However,to determine the crystal structure of conjugated polymers is a significant challenge,mainly due to the poor crystallinity,weak diffraction,and instability under high-energy radiation.Here,we build the possible crystal structures of eight typical conjugated polymers,covering several widely used molecular segments in organic optoelectronics.We model the packing structures of these seed polymers based on synchrotron X-ray diffractions and molecular simulations.These crystal structures provide a new platform to predict the packing structures of more related polymer systems,extending the molecular scope.Based on this polymer crystal structure database,the multiscale microstructures and charge transport properties of conjugated polymers can be predicted before experiments.This study sets up a polymer crystal structure database to eliminate the current trial-and-error approaches and accelerating the design of high-performance conjugated polymers.展开更多
Diesel molecular compositional model has important application for diesel quality prediction,blending,and molecular-level process model development.In this paper,different types of diesel molecular compositional and b...Diesel molecular compositional model has important application for diesel quality prediction,blending,and molecular-level process model development.In this paper,different types of diesel molecular compositional and blending models were constructed based on the SU-BEM framework.More than 1500 representative molecules were selected to form the molecular structure library.The probability density functions(PDFs)combination was determined by experimental data and experience.A quadratic optimization strategy combining genetic algorithm with local optimization algorithm was adopted to improve the accuracy of the compositional model.The model results show good agreement with the experimental data.The diesel blending model was constructed at the molecular-level based on the above diesel compositional models.The properties of the blending model accord with the experimental regulations.It is proved that the compositional models and blending model constructed have high accuracy and strong prediction capability,and are applicable to the industrial process.展开更多
BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic ...BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic gains.Chitin-glucan(CG)is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority.To provide an alternative approach to managing patients with IBS,we performed preclinical molecular,cellular,and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS.AIM To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular models.METHODS Visceral pain was recorded through colorectal distension(CRD)in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS[15 milligrams(mg)/kilogram(kg)]in 33 Sprague-Dawley rats.Intracolonic pressure was regularly assessed during the 9 wk-experiment(weeks 0,3,5,and 7)in animals receiving CG(n=14)at a human equivalent dose(HED)of 1.5 g/d or 3.0 g/d and compared to negative control(tap water,n=11)and positive control(phloroglucinol at 1.5 g/d HED,n=8)groups.The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate(DSS)administered in their drinking water during 14 d.HT-29 cells under basal conditions and after stimulation with lipopolysaccharide(LPS)were treated with CG to evaluate changes in pathways related to analgesia μ-opioid receptor(MOR),cannabinoid receptor 2(CB2),peroxisome proliferator-activated receptor alpha,inflammation[interleukin(IL)-10,IL-1b,and IL-8]and barrier function[mucin 2-5AC,claudin-2,zonula occludens(ZO)-1,ZO-2]using the real-time PCR method.Molecular modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations.Data were expressed as the mean±SEM.RESULTS Daily CG orally-administered to rats or mice was well tolerated without including diarrhea,visceral hypersensitivity,or inflammation,as evaluated at histological and molecular levels.In a model of CRD,CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14%after 2 wk of administration(P<0.01)and reduced inflammation intensity by 50%,resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis.To better reproduce the characteristics of visceral pain in patients with IBS,we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity.CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20%five weeks after colitis induction(P<0.01).When the CG dosage was increased to 3.0 g/d HED,this analgesic effect surpassed that of the spasmolytic agent phloroglucinol,manifesting more rapidly within 3 wk and leading to a 50%inhibition of pain perception(P<0.0001).The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved,at least in part,a significant induction of MOR,CB2 receptor,and IL-10,as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8.CG also significantly upregulated barrier-related genes including muc5AC,claudin-2,and ZO-2.Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids,sequestering gram-negative LPS and gram-positive LTA bacterial toxins,as well as PLM in fungi at the lowesr energy conformations.CONCLUSION CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products,suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBSlike symptoms.展开更多
High levels of the neurotoxic beta-amyloid protein (A<em>β</em>) in patients with Alzheimer’s disease present a significant therapeutic target, although the protein is unlikely to be the sole instigator ...High levels of the neurotoxic beta-amyloid protein (A<em>β</em>) in patients with Alzheimer’s disease present a significant therapeutic target, although the protein is unlikely to be the sole instigator of this condition. A<em>β</em> initiates cell receptor and synapse dysfunction, and causes mitochondrial damage within neurons. Neurotransmitters and various small molecular weight compounds ameliorate the effects of A<em>β</em> on cell membranes. This study uses a molecular modeling technique to compare the structures of A<em>β</em>25-35 and compounds known to antagonize properties of the polypeptide. Compounds provide good fits to the peptide amino acid residues, revealing planarity in their linear structures and fitting points. Compounds and polypeptide share relative molecular similarity, affinity for receptors and apoptosis modulating properties indicative of their potential for competition at neuron membrane sites. The therapeutic targeting of A<em>β</em> by small molecular weight compounds may benefit from a multi-drug approach.展开更多
This work presents a study of intermolecular interactions using the model of the antigen antibody interactions of the ABO system. Absence of knowledge in the field of the ABO antigen’s behavior as a biomolecule and t...This work presents a study of intermolecular interactions using the model of the antigen antibody interactions of the ABO system. Absence of knowledge in the field of the ABO antigen’s behavior as a biomolecule and the integration of these structures into cascade of metabolic and physiological processes create the conditions, which promote a successful using this new model in the future. Molecular recognition and designing are included into the main catalog of computer methods of research, which is called “in silico”. Using PASS system, we describe the possible biological effects of pyruvate, lactate, antigen determinants A and B. Pharmacological effects and molecular mechanisms of influence on activity of the factors regulating inside and intercellular interactions are predicted for such minor components as pyruvate and lactate. Due to variety of the biological effects, glycoproteins A and B are very perspective to study as biological active connections. The obtained knowledge proves that AB0 antigens, as well as other glycoprotein conjugates are important mediators of intercellular adhesion and participants of signal transmission. Using ABO blood group system as a model helped to describe individual differences of parameters—degree and time of the agglutination beginning of antigen/antibody blood types of the AB0—are revealed.展开更多
In this study, the chiral separation mechanisms of Dansyl amino acids, including Dansyl-Leucine (Dans-Leu), Dansyl-Norleucine (Dans-Nor), Dansyl-Tryptophan (Dans-Trp) and Dansyl-Phenylalanine (Dans-Phe) binding to pol...In this study, the chiral separation mechanisms of Dansyl amino acids, including Dansyl-Leucine (Dans-Leu), Dansyl-Norleucine (Dans-Nor), Dansyl-Tryptophan (Dans-Trp) and Dansyl-Phenylalanine (Dans-Phe) binding to poly-sodium </span><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">N</span></i><i><span style="font-family:Verdana;"></i></span></i><span style="font-family:Verdana;">-undecanoyl-(L)-Leucylvalinate, poly (SULV), were investigated using molecular dynamics simulations. Micellar electrokinetic chromatography (MEKC) has previously shown that when separating the enantiomers of these aforementioned Dansyl amino acids, the L-enantiomers bind stronger to poly (SULV) than the D-enantiomers. This study aims to investigate the molecular interactions that govern chiral recognition in these systems using computational methods. This study reveals that the computationally-calculated binding free energy values for Dansyl enantiomers binding to poly (SULV) are in agreement with the enantiomeric order produced in experimental MEKC studies. The L-enantiomers of Dans-Leu, Dans-Nor, Dans-Trp, and Dans-Phe binding to their preferred binding pockets in poly (SULV) yielded binding free energy values of </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">21.8938, </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">22.1763, </span><span style="font-family:Verdana;">-</span><span style="font-family:""><span style="font-family:Verdana;">21.3329 </span><span style="font-family:Verdana;">and </span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">13.3349 kJ</span><span style="font-family:Verdana;">·</span><span style="font-family:Verdana;">mol</span><sup><span style="font-family:Verdana;">-</span></sup><sup><span style="font-family:Verdana;">1</span></sup><span style="font-family:Verdana;">, respectively. The D-enantiomers of Dans-Leu, Dans-Nor</span><span style="font-family:Verdana;">, Dans-Trp, and Dans-Phe binding to their preferred binding pockets in poly (SULV) yielded binding free energy values of </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">14.5811, </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">15.9457, </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">13.6408, and </span><span style="font-family:Verdana;">-</span><span style="font-family:""><span style="font-family:Verdana;">12.0959</span><b> </b><span style="font-family:Verdana;">kJ</span></span><span style="font-family:Verdana;">·</span><span style="font-family:Verdana;">mol</span><sup><span style="font-family:Verdana;">-</span></sup><sup><span style="font-family:Verdana;">1</span></sup><span style="font-family:Verdana;">, respectively. Furthermore, hydrogen bonding analyses w</span><span style="font-family:Verdana;">ere</span><span style="font-family:Verdana;"> used to investigate and elucidate the molecular interactions that govern chiral recognition in these molecular systems.展开更多
This study was aimed to investigate Pb(II) and Cu(II) ions removal ability from aqueous solution by cassava root husks (CRH) as a cheap, sustainable and eco<span>-</span><span><span>friendly bi...This study was aimed to investigate Pb(II) and Cu(II) ions removal ability from aqueous solution by cassava root husks (CRH) as a cheap, sustainable and eco<span>-</span><span><span>friendly bioadsorbent. The CRH was characterized by Fourier Transform Infrared (FTIR) spectroscopy which indicated the availability of various functional groups for metal coordination and the result was supported by elemental analysis studies. UV-Visible spectral studies indicated the presence of oxalate (</span><img src="Edit_88f5f86a-6e96-4764-8dc0-31bbb7ac83c6.png" width="34" height="18" alt="" /></span><span><span></span><span><span>) </span><span>and it could possibly interact with metal ions to give rise to a stable chelated coordination complex which affects metal ions removal efficiency. Bioadsorption process was carried out as a function of metal concentration, contact time, pH of the solution, particle size</span></span><span>,</span><span> and dosage of the adsorbent. Experimental results indicated the optimal adsorption condition of pH 4 for both Pb(II) and Cu(II) ions, dosage of 0.1</span><span style="font-family:;" "=""> </span><span>g/0.1L and 1</span><span style="font-family:;" "=""> </span><span>g/0.1L for Pb(II) and Cu(II) ions respectively, adsorption equilibrium time of 2 and 25 minutes for Pb(II) and Cu(II) respectively, and concentration of 0.5 mg/L for both metal ions. Kinetic data best</span><span style="font-family:;" "=""> </span><span>fitted pseudo-second-order model and not </span><span>the </span><span>pseudo-first-order model. Equilibrium data best fitted </span><span>the </span><span>Freundlich model than </span><span>the </span><span>Langmuir model. Specific surface area and pore volume studies indicated that CRH is non-porous and hence rapid adsorption kinetics is expected. Supporting the experimental results, molecular modeling studies performed using Schr<span style="white-space:nowrap;">ö</span>dinger software predicted several sites in the structure capable of docking with metal ions.</span></span>展开更多
In the article a molecular model of oil with nanoparticles on the basis of the model of ideal fluid is considered. It is assumed that the molecular model of the oil can be represented as a homogenous distribution of i...In the article a molecular model of oil with nanoparticles on the basis of the model of ideal fluid is considered. It is assumed that the molecular model of the oil can be represented as a homogenous distribution of identical molecules in space. It is assumed that the central interaction between the oil molecules and nanoparticles, results in a change of the model parameters. It is shown that for an ideal fluid the effect of nanoparticles is reduced to a change of the coefficient at the pressure.展开更多
BACKGROUND Leprosy is a disease caused by Mycobacterium leprae(M.leprae),an intracellular pathogen that has tropism and affects skin and nervous system cells.The disease has two forms of presentation:Paucibacillary an...BACKGROUND Leprosy is a disease caused by Mycobacterium leprae(M.leprae),an intracellular pathogen that has tropism and affects skin and nervous system cells.The disease has two forms of presentation:Paucibacillary and multibacillary,with different clinical and immunological manifestations.Unlike what occurs in the multibacillary form,the diagnostic tests for the paucibacillary form are nonspecific and not very sensitive,allowing the existence of infected individuals without treatment,which contributes to the spread of the pathogen in the population.To mitigate this contamination,more sensitive diagnostic tests capable of detecting paucibacillary patients are needed.AIM To predict the three-dimensional structure models of M.leprae antigens with serodiagnostic potential for leprosy.METHODS In this in silico study,satisfactory templates were selected in the Protein Data Bank(PDB)using Basic Local Alignment Search Tool to predict the structural templates of ML2038,ML0286,ML0050,and 85B antigens by comparative modeling.The templates were selected according to general criteria such as sequence identity,coverage,X-ray resolution,Global Model Quality Estimate value and phylogenetic relationship;Clustal X 2.1 software was used in this analysis.Molecular modeling was completed using the software Modeller 9v13.Visualization of the models was made using ViewerLite 4.2 and PyMol software,and analysis of the quality of the predicted models was performed using the QMEAN score and Z-score.Finally,the three-dimensional moels were validated using the MolProbity and Verify 3D platforms.RESULTS The three-dimensional structure models of ML2038,ML0286,ML0050,and 85B antigens of M.leprae were predicted using the templates PDB:3UOI(90.51%identity),PDB:3EKL(87.46%identity),PDB:3FAV(40.00%identity),and PDB:1F0N(85.21%identity),respectively.The QMEAN and Z-score values indicated the good quality of the structure models.These data refer to the monomeric units of antigens,since some of these antigens have quaternary structure.The validation of the models was performed with the final three-dimensional structure-monomer(ML0050 and 85B antigens)and quaternary structures(ML2038 and ML0286).The majority of amino acid residues were observed in favorable and allowed regions in the Ramachandran plot,indicating correct positioning of the side chain and absence of steric impediment.The MolProbity score value and Verify 3D results of all models indicated a satisfactory prediction.CONCLUSION The polarized immune response against M.leprae creates a problem in leprosy detection.The selection of immunodominant epitopes is essential for the development of more sensitive serodiagnostic tests,for this it is important to know the three-dimensional structure of the antigens,which can be predicted with bioinformatics tools.展开更多
The treatment and disposal of radioactive waste are presently facing great challenges.Spent ion exchange resins have become a focus of attention due to their high production and serious environmental risks.In this pap...The treatment and disposal of radioactive waste are presently facing great challenges.Spent ion exchange resins have become a focus of attention due to their high production and serious environmental risks.In this paper,a simplified model of cationic exchange resin is proposed,and the degradation processes of cationic resin monomer initiated by hydroxyl radicals(·OH)are clarified by combining statistical molecular fragmentation(SMF)model and density functional theory(DFT)calculations.The prediction of active sites indicates that the S-O bonds and the C-S bond of the sulfonic group are more likely to react during the degradation.The meta-position of the sulfonic group on the benzene ring is the most active site,and the benzene ring without the sulfonic group has a certain reactivity.The C11-C14 and C17-C20 bonds,on the carbon skeleton,are the most easily broken.It is also found that dihydroxy addition and elimination reactions play a major role in the process of desulfonation,carbon skeleton cleavage and benzene ring separation.The decomposition mechanisms found through the combination of physical models and chemical calculations,provide theoretical guidance for the treatment of complex polycyclic aromatic hydrocarbons.展开更多
Understanding and modulating the interaction between various reactive molecules and oxygen carriers are the key issue to achieve process intensification of chemical looping technology.C1 chemical molecules play an imp...Understanding and modulating the interaction between various reactive molecules and oxygen carriers are the key issue to achieve process intensification of chemical looping technology.C1 chemical molecules play an important role in many reactions involved with chemical looping processes.However,up to now,there is still a lack of systematic and in-depth understanding of the adsorption mechanism of C1 molecules on the surface of oxygen carriers(OCs).In this work,the intrinsic interaction between a series of C1 molecules composed of CH4,CO,CO2,CH3OH,HCHO and HCOOH and surface of Ni O OCs in the chemical looping process have been studied using density functional theory calculations.Various adsorption configurations of C1 molecules and also different adsorption sites of Ni O have been considered.The structural features of stable configuration of C1 molecules on the surface of NiO OCs have been obtained.Further,the interacted sites,types and strengths of C1 molecules on the surface of NiO have been directly pictured by the independent gradient model methods.Also,the nature of the interaction between C1 molecule and Ni O surface has been investigated with the aid of energy decomposition analysis from a quantitative view.展开更多
Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin recept...Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin receptors(5-HTRs), which is a promising tool in the determination of the receptor’s function and relationship with the diseases related to serotonin and its receptor dysfunction. Serotonin was effectively labeled via a direct electrophilic substitutional reaction using an oxidizing agent such as iodogen with 125I in a neutral medium, and 125I-serotonin was achieved with a maximum labeling yield of 91 ± 0.63% with in vitro stability up to 24 h. Molecular modeling was conducted to signify 125I-serotonin structure and confirm that the radiolabeling process did not affect serotonin binding ability to its receptors. Biodistribution studies show that the maximum gastro intestinal tract uptake of 125I-serotonin was 17.8 ± 0.93% ID/organ after 30 min postinjection and the tracer’s ability to pass the blood–brain barrier. Thus, 125I-serotonin is a promising single photon emission computed tomography tracer in the detection of 5 HTRs.展开更多
Cdc25 phosphatase have been regarded as attractive drug targets for anticancer therapies due to the correlation of their over expression with a wide variety of cancers. They are key regulators of cell cycle progressio...Cdc25 phosphatase have been regarded as attractive drug targets for anticancer therapies due to the correlation of their over expression with a wide variety of cancers. They are key regulators of cell cycle progression and play a central role in the checkpoint response to DNA damage. The role of Cdc25 s in cancer has become increasingly evident in recent years. More than 20 studies of patient samples are from diverse cancers show significant overexpression of Cdc25 with frequent correlation to clinical outcome. Recent screening and design efforts have yielded novel classes of inhibitors that show specificity for the Cdc25 s over other phosphatases and cause cell cycle arrest in vivo. Until now, quinone derivatives are among the most efficient inhibitors of Cdc25 phosphatase activity. Our research objective is to study the inhibition of the phosphathase Cdc25 through the molecular modeling methods.展开更多
基金supported by the Multi-Year Research Grants from the University of Macao(MYRG2019-00032-ICMS and MYRG2020-00113-ICMS)the Macao FDCT research grant(0108/2021/A)Molecular modeling was performed at the High-Performance Computing Cluster(HPCC),which is supported by the Information and Communication Technology Office(ICTO)of the University of Macao.
文摘Liposome is one of the most widely used carriers for drug delivery because of the great biocompatibility and biodegradability.Due to the complex formulation components and preparation process,formulation screening mostly relies on trial-and-error process with low efficiency.Here liposome formulation prediction models have been built by machine learning(ML)approaches.The important parameters of liposomes,including size,polydispersity index(PDI),zeta potential and encapsulation,are predicted individually by optimal ML algorithm,while the formulation features are also ranked to provide important guidance for formulation design.The analysis of key parameter reveals that drug molecules with logS[-3,-6],molecular complexity[500,1000]and XLogP3(≥2)are priority for preparing liposome with higher encapsulation.In addition,naproxen(NAP)and palmatine HCl(PAL)represented the insoluble and water-soluble molecules are prepared as liposome formulations to validate prediction ability.The consistency between predicted and experimental value verifies the satisfied accuracy of ML models.As the drug properties are critical for liposome particles,the molecular interactions and dynamics of NAP and PAL liposome are further investigated by coarse-grained molecular dynamics simulations.The modeling structure reveals that NAP molecules could distribute into lipid layer,while most PAL molecules aggregate in the inner aqueous phase of liposome.The completely different physical state of NAP and PAL confirms the importance of drug properties for liposome formulations.In summary,the general prediction models are built to predict liposome formulations,and the impacts of key factors are analyzed by combing ML with molecular modeling.The availability and rationality of these intelligent prediction systems have been proved in this study,which could be applied for liposome formulation development in the future.
基金supported by the Jiangsu Provincial Key Research and Development Program (Grant No.BE2020616)the National Key R&D Program of China (Grant No.2018YFC1200603)+1 种基金the National Science and Technology Major Project (Grant No.2019SWAQ05-5-4)Jiangsu Key Lab of Cancer Biomarkers,Prevention and Treatment,Collaborative Innovation Center for Cancer Personalized Medicine,Nanjing Medical University.
文摘Although vaccines have been developed,mutations of SARS-CoV-2,especially the dominant B.1.617.2(delta)and B.1.529(omicron)strains with more than 30 mutations on their spike protein,have caused a significant decline in prophylaxis,calling for the need for drug improvement.Antibodies are drugs preferentially used in infectious diseases and are easy to get from immunized organisms.The current study combined molecular modeling and single memory B cell sequencing to assess candidate sequences before experiments,providing a strategy for the fabrication of SARS-CoV-2 neutralizing antibodies.A total of 128 sequences were obtained after sequencing 196 memory B cells,and 42 sequences were left after merging extremely similar ones and discarding incomplete ones,followed by homology modeling of the antibody variable region.Thirteen candidate sequences were expressed,of which three were tested positive for receptor binding domain recognition but only one was confirmed as having broad neutralization against several SARS-CoV-2 variants.The current study successfully obtained a SARS-CoV-2 antibody with broad neutralizing abilities and provided a strategy for antibody development in emerging infectious diseases using single memory B cell BCR sequencing and computer assistance in antibody fabrication.
文摘A novel ligand N-4-hydroxyacetophenone isonicotinoyl hydrazone and its manganese(II) and nickel(II) metal complexes have been synthesized. The synthesized Schiff base and its metal complexes have been characterized by physical state determination, melting point and solubility measurements in different solvents, infrared, proton nuclear magnetic resonance, mass spectrometric and powder X-ray spectroscopic techniques. The thermal properties of the prepared compounds were obtained from TG/DTG measurements. On the basis of the analytical techniques, the ligand was found to be bidentate in nature coordinating to the metal ions through the azomethine nitrogen and carbonyl oxygen atoms leading to distorted octahedral geometries of the metal complexes which were modeled using MM2 force field. The ligand and its metal(II) complexes were evaluated for antifungal activity against <i>Aspergillus fumigatus, Aspergillus niger, Candida albicans and Rhizopus stolonifera.</i> The antifungal evaluation results revealed an enhanced activity upon coordination of the ligand with the metal(II) ions. The activity of the metal complex to the tested fungal strains was in the order Ni(II) > Mn(II).
基金the National Autonomous University of Mexico for financial support(grant DGAPA-IN100303)A.H.thanks the National Council of Science and Technology of Mexico(CONACyT)and DAAD for scholarships
文摘An insight into the interaction of collagen type I with apatite in bone tissue was performed by using differential scanning calorimetry, Fourier transform infrared spectroscopy, and molecular modeling. Scanning electron microscopy shows that bone organic content incinerate gradually through the different temperatures studied. We suggest that the amide regions of the type I collagen molecule (mainly C=O groups of the peptide bonds) will be important in the control of the interactions with the apatite from bone. The amide I infrared bands of the collagen type I change when interacting to apatite, what might confirm our assumption. Bone tissue results in a loss of thermal stability compared to the collagen studied apart, as a consequence of the degradation and further combustion of the collagen in contact with the apatite microcrystals in bone. The thermal behavior of bone is very distinctive. Its main typical combustion temperature is at 360°C with a shoulder at 550°C compared to the thermal behavior of collagen, with the mean combustion peak at ca. 500°C. Our studies with molecular mechanics (MM+ force field) showed different interaction energies of the collagen-like molecule and different models of the apatite crystal planes. We used models of the apatite (100) and (001) planes;additional two planes (001) were explored with phosphate-rich and calcium-rich faces;an energetic preference was found in the latter case. We preliminary conclude that the peptide bond of collagen type I is modified when the molecule interacts with the apatite, producing a decrease in the main peak from ca. 500°C in collagen, up to 350°C in bone. The combustion might be related to collagen type I, as the ΔH energies present only small variations between mineralized and non-mineralized samples. The data obtained here give a molecular perspective into the structural properties of bone and the change in collagen properties caused by the interaction with the apatite. Our study can be useful to understand the biological synthesis of minerals as well as the organic-inorganic interaction and the synthesis of apatite implant materials.
基金Proyect:PAPIIT IT200817PAPIIT No 202015Catedra PIAPI1607:Diseno de moleculas bioativas.
文摘Carbamates are molecules that have different types of biological activities and provide a particular chemical control against ticks. The new structures of the proposed compounds were optimized and synthetized respectively, through a molecular model using the methods:PM3, HF and DFT applying the B3LYP functional, with the basis 6-31+G(d) and 6-311+G(d,p), BVP86 and PBEPBE with 6-31+G(d) and the vibrational frequencies computed. These calculated frequencies were compared with the experimental ones to determine the most accurate level of theory for the prediction of vibrational frequencies of the compounds. The best results were obtained through HF/631+G(d). Additionally, we report a modification to obtain this type of compounds, and based on the amino-dehalogenation of ethyl chloroformate, different benzyl ethyl carbamates were synthesized modifying the base molecule. The performances obtained were compared to others already reported. The methodology used allowed us to synthesize new carbamates using benzylamine derivatives through a modification on the basic catalysis of the addition-elimination reaction.
基金supported by the National Natural Science Foundation of China(Grant No.30470408).
文摘Aggregation of amyloid ?-peptide (A?) into insoluble fibrils is a key pathological event in Alzheimer’s disease (AD). Under certain conditions, Cu(II) exhibits strong inhibitory ef-fect on the Zn(II)-induced aggregation, which occurs significantly even at nearly physiological concentrations of zinc ion in vitro. Cu(II) is considered as a potential factor in the normal brain preventing A? from aggregating. The possible mechanism of the inhibitory effect of Cu(II) is in-vestigated for the first time by molecular modeling method. In the mono-ring mode, the Y10 residue promotes typical quasi-helix conformations of A?. Specially, [Cu-H13(Np)-Y10(OH)] complex forms a local 3.010 helix conformation. In the multi-ring mode, the side chains of Q15 and E11 residues collaborate harmoniously with other chelating ligands producing markedly low energies and quasi-helix conformations. [Cu-3N-Q15(O)-E11(O1)] and [Cu-H13(Np)-Y10(OH)] complex with quasi-helix conformations may prefer soluble forms in solution. In addition, hydro-gen-bond interactions may be the main driving force for A? aggregation. All the results will pro-vide helpful clues for an improved understanding of the role of Cu(II) in the pathogenesis of AD and contribute to the development of an “anti-amyloid” therapeutic strategy.
基金part by 973 program(2012C B911102)the National S&T Major Special Project on Major New Drug Innovation(2012ZX09102101-018)the National S&T International Collaboration 2010DFA31580(J.D.J.)and 2010DFB30870(Q.J.).
文摘APOBEC3G(A3G)is a host cytidine deaminase that incorporates into HIV-1 virions and efficiently inhibits viral replication.The virally encoded protein Vif binds to A3G and induces its degradation,thereby counteracting the antiviral activity of A3G.Vif-mediated A3G degradation clearly represents a potential target for anti-HIV drug development.Currently,there is an urgent need for understanding the three dimensional structure of full-length A3G.In this work,we use a homology modeling approach to propose a structure for A3G based on the crystal structure of APOBEC2(APO2)and the catalytic domain structure of A3G.Two compounds,IMB26 and IMB35,which have been shown to bind to A3G and block degradation by Vif,were docked into the A3G model and the binding modes were generated for further analysis.The results may be used to design or optimize molecules targeting Vif–A3G interaction,and lead to the development of novel anti-HIV drugs.
基金supported by National Key R&D Program of China(2017YFA0204701)National Natural Science Foundation of China(21420102005,21790360,21722201)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910001001).
文摘Crystal structure of conjugated molecules and polymers is fundamentally critical to understand their multilevel microstructures,carrier transport,and diverse functions.However,to determine the crystal structure of conjugated polymers is a significant challenge,mainly due to the poor crystallinity,weak diffraction,and instability under high-energy radiation.Here,we build the possible crystal structures of eight typical conjugated polymers,covering several widely used molecular segments in organic optoelectronics.We model the packing structures of these seed polymers based on synchrotron X-ray diffractions and molecular simulations.These crystal structures provide a new platform to predict the packing structures of more related polymer systems,extending the molecular scope.Based on this polymer crystal structure database,the multiscale microstructures and charge transport properties of conjugated polymers can be predicted before experiments.This study sets up a polymer crystal structure database to eliminate the current trial-and-error approaches and accelerating the design of high-performance conjugated polymers.
基金supported by the SINOPEC R&D Program(grant number 119014-1)
文摘Diesel molecular compositional model has important application for diesel quality prediction,blending,and molecular-level process model development.In this paper,different types of diesel molecular compositional and blending models were constructed based on the SU-BEM framework.More than 1500 representative molecules were selected to form the molecular structure library.The probability density functions(PDFs)combination was determined by experimental data and experience.A quadratic optimization strategy combining genetic algorithm with local optimization algorithm was adopted to improve the accuracy of the compositional model.The model results show good agreement with the experimental data.The diesel blending model was constructed at the molecular-level based on the above diesel compositional models.The properties of the blending model accord with the experimental regulations.It is proved that the compositional models and blending model constructed have high accuracy and strong prediction capability,and are applicable to the industrial process.
基金Supported by the Service Public de Wallonie(SPW-EER,convention 8588,Belgium).
文摘BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic gains.Chitin-glucan(CG)is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority.To provide an alternative approach to managing patients with IBS,we performed preclinical molecular,cellular,and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS.AIM To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular models.METHODS Visceral pain was recorded through colorectal distension(CRD)in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS[15 milligrams(mg)/kilogram(kg)]in 33 Sprague-Dawley rats.Intracolonic pressure was regularly assessed during the 9 wk-experiment(weeks 0,3,5,and 7)in animals receiving CG(n=14)at a human equivalent dose(HED)of 1.5 g/d or 3.0 g/d and compared to negative control(tap water,n=11)and positive control(phloroglucinol at 1.5 g/d HED,n=8)groups.The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate(DSS)administered in their drinking water during 14 d.HT-29 cells under basal conditions and after stimulation with lipopolysaccharide(LPS)were treated with CG to evaluate changes in pathways related to analgesia μ-opioid receptor(MOR),cannabinoid receptor 2(CB2),peroxisome proliferator-activated receptor alpha,inflammation[interleukin(IL)-10,IL-1b,and IL-8]and barrier function[mucin 2-5AC,claudin-2,zonula occludens(ZO)-1,ZO-2]using the real-time PCR method.Molecular modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations.Data were expressed as the mean±SEM.RESULTS Daily CG orally-administered to rats or mice was well tolerated without including diarrhea,visceral hypersensitivity,or inflammation,as evaluated at histological and molecular levels.In a model of CRD,CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14%after 2 wk of administration(P<0.01)and reduced inflammation intensity by 50%,resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis.To better reproduce the characteristics of visceral pain in patients with IBS,we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity.CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20%five weeks after colitis induction(P<0.01).When the CG dosage was increased to 3.0 g/d HED,this analgesic effect surpassed that of the spasmolytic agent phloroglucinol,manifesting more rapidly within 3 wk and leading to a 50%inhibition of pain perception(P<0.0001).The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved,at least in part,a significant induction of MOR,CB2 receptor,and IL-10,as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8.CG also significantly upregulated barrier-related genes including muc5AC,claudin-2,and ZO-2.Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids,sequestering gram-negative LPS and gram-positive LTA bacterial toxins,as well as PLM in fungi at the lowesr energy conformations.CONCLUSION CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products,suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBSlike symptoms.
文摘High levels of the neurotoxic beta-amyloid protein (A<em>β</em>) in patients with Alzheimer’s disease present a significant therapeutic target, although the protein is unlikely to be the sole instigator of this condition. A<em>β</em> initiates cell receptor and synapse dysfunction, and causes mitochondrial damage within neurons. Neurotransmitters and various small molecular weight compounds ameliorate the effects of A<em>β</em> on cell membranes. This study uses a molecular modeling technique to compare the structures of A<em>β</em>25-35 and compounds known to antagonize properties of the polypeptide. Compounds provide good fits to the peptide amino acid residues, revealing planarity in their linear structures and fitting points. Compounds and polypeptide share relative molecular similarity, affinity for receptors and apoptosis modulating properties indicative of their potential for competition at neuron membrane sites. The therapeutic targeting of A<em>β</em> by small molecular weight compounds may benefit from a multi-drug approach.
文摘This work presents a study of intermolecular interactions using the model of the antigen antibody interactions of the ABO system. Absence of knowledge in the field of the ABO antigen’s behavior as a biomolecule and the integration of these structures into cascade of metabolic and physiological processes create the conditions, which promote a successful using this new model in the future. Molecular recognition and designing are included into the main catalog of computer methods of research, which is called “in silico”. Using PASS system, we describe the possible biological effects of pyruvate, lactate, antigen determinants A and B. Pharmacological effects and molecular mechanisms of influence on activity of the factors regulating inside and intercellular interactions are predicted for such minor components as pyruvate and lactate. Due to variety of the biological effects, glycoproteins A and B are very perspective to study as biological active connections. The obtained knowledge proves that AB0 antigens, as well as other glycoprotein conjugates are important mediators of intercellular adhesion and participants of signal transmission. Using ABO blood group system as a model helped to describe individual differences of parameters—degree and time of the agglutination beginning of antigen/antibody blood types of the AB0—are revealed.
文摘In this study, the chiral separation mechanisms of Dansyl amino acids, including Dansyl-Leucine (Dans-Leu), Dansyl-Norleucine (Dans-Nor), Dansyl-Tryptophan (Dans-Trp) and Dansyl-Phenylalanine (Dans-Phe) binding to poly-sodium </span><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">N</span></i><i><span style="font-family:Verdana;"></i></span></i><span style="font-family:Verdana;">-undecanoyl-(L)-Leucylvalinate, poly (SULV), were investigated using molecular dynamics simulations. Micellar electrokinetic chromatography (MEKC) has previously shown that when separating the enantiomers of these aforementioned Dansyl amino acids, the L-enantiomers bind stronger to poly (SULV) than the D-enantiomers. This study aims to investigate the molecular interactions that govern chiral recognition in these systems using computational methods. This study reveals that the computationally-calculated binding free energy values for Dansyl enantiomers binding to poly (SULV) are in agreement with the enantiomeric order produced in experimental MEKC studies. The L-enantiomers of Dans-Leu, Dans-Nor, Dans-Trp, and Dans-Phe binding to their preferred binding pockets in poly (SULV) yielded binding free energy values of </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">21.8938, </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">22.1763, </span><span style="font-family:Verdana;">-</span><span style="font-family:""><span style="font-family:Verdana;">21.3329 </span><span style="font-family:Verdana;">and </span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">13.3349 kJ</span><span style="font-family:Verdana;">·</span><span style="font-family:Verdana;">mol</span><sup><span style="font-family:Verdana;">-</span></sup><sup><span style="font-family:Verdana;">1</span></sup><span style="font-family:Verdana;">, respectively. The D-enantiomers of Dans-Leu, Dans-Nor</span><span style="font-family:Verdana;">, Dans-Trp, and Dans-Phe binding to their preferred binding pockets in poly (SULV) yielded binding free energy values of </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">14.5811, </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">15.9457, </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">13.6408, and </span><span style="font-family:Verdana;">-</span><span style="font-family:""><span style="font-family:Verdana;">12.0959</span><b> </b><span style="font-family:Verdana;">kJ</span></span><span style="font-family:Verdana;">·</span><span style="font-family:Verdana;">mol</span><sup><span style="font-family:Verdana;">-</span></sup><sup><span style="font-family:Verdana;">1</span></sup><span style="font-family:Verdana;">, respectively. Furthermore, hydrogen bonding analyses w</span><span style="font-family:Verdana;">ere</span><span style="font-family:Verdana;"> used to investigate and elucidate the molecular interactions that govern chiral recognition in these molecular systems.
文摘This study was aimed to investigate Pb(II) and Cu(II) ions removal ability from aqueous solution by cassava root husks (CRH) as a cheap, sustainable and eco<span>-</span><span><span>friendly bioadsorbent. The CRH was characterized by Fourier Transform Infrared (FTIR) spectroscopy which indicated the availability of various functional groups for metal coordination and the result was supported by elemental analysis studies. UV-Visible spectral studies indicated the presence of oxalate (</span><img src="Edit_88f5f86a-6e96-4764-8dc0-31bbb7ac83c6.png" width="34" height="18" alt="" /></span><span><span></span><span><span>) </span><span>and it could possibly interact with metal ions to give rise to a stable chelated coordination complex which affects metal ions removal efficiency. Bioadsorption process was carried out as a function of metal concentration, contact time, pH of the solution, particle size</span></span><span>,</span><span> and dosage of the adsorbent. Experimental results indicated the optimal adsorption condition of pH 4 for both Pb(II) and Cu(II) ions, dosage of 0.1</span><span style="font-family:;" "=""> </span><span>g/0.1L and 1</span><span style="font-family:;" "=""> </span><span>g/0.1L for Pb(II) and Cu(II) ions respectively, adsorption equilibrium time of 2 and 25 minutes for Pb(II) and Cu(II) respectively, and concentration of 0.5 mg/L for both metal ions. Kinetic data best</span><span style="font-family:;" "=""> </span><span>fitted pseudo-second-order model and not </span><span>the </span><span>pseudo-first-order model. Equilibrium data best fitted </span><span>the </span><span>Freundlich model than </span><span>the </span><span>Langmuir model. Specific surface area and pore volume studies indicated that CRH is non-porous and hence rapid adsorption kinetics is expected. Supporting the experimental results, molecular modeling studies performed using Schr<span style="white-space:nowrap;">ö</span>dinger software predicted several sites in the structure capable of docking with metal ions.</span></span>
文摘In the article a molecular model of oil with nanoparticles on the basis of the model of ideal fluid is considered. It is assumed that the molecular model of the oil can be represented as a homogenous distribution of identical molecules in space. It is assumed that the central interaction between the oil molecules and nanoparticles, results in a change of the model parameters. It is shown that for an ideal fluid the effect of nanoparticles is reduced to a change of the coefficient at the pressure.
文摘BACKGROUND Leprosy is a disease caused by Mycobacterium leprae(M.leprae),an intracellular pathogen that has tropism and affects skin and nervous system cells.The disease has two forms of presentation:Paucibacillary and multibacillary,with different clinical and immunological manifestations.Unlike what occurs in the multibacillary form,the diagnostic tests for the paucibacillary form are nonspecific and not very sensitive,allowing the existence of infected individuals without treatment,which contributes to the spread of the pathogen in the population.To mitigate this contamination,more sensitive diagnostic tests capable of detecting paucibacillary patients are needed.AIM To predict the three-dimensional structure models of M.leprae antigens with serodiagnostic potential for leprosy.METHODS In this in silico study,satisfactory templates were selected in the Protein Data Bank(PDB)using Basic Local Alignment Search Tool to predict the structural templates of ML2038,ML0286,ML0050,and 85B antigens by comparative modeling.The templates were selected according to general criteria such as sequence identity,coverage,X-ray resolution,Global Model Quality Estimate value and phylogenetic relationship;Clustal X 2.1 software was used in this analysis.Molecular modeling was completed using the software Modeller 9v13.Visualization of the models was made using ViewerLite 4.2 and PyMol software,and analysis of the quality of the predicted models was performed using the QMEAN score and Z-score.Finally,the three-dimensional moels were validated using the MolProbity and Verify 3D platforms.RESULTS The three-dimensional structure models of ML2038,ML0286,ML0050,and 85B antigens of M.leprae were predicted using the templates PDB:3UOI(90.51%identity),PDB:3EKL(87.46%identity),PDB:3FAV(40.00%identity),and PDB:1F0N(85.21%identity),respectively.The QMEAN and Z-score values indicated the good quality of the structure models.These data refer to the monomeric units of antigens,since some of these antigens have quaternary structure.The validation of the models was performed with the final three-dimensional structure-monomer(ML0050 and 85B antigens)and quaternary structures(ML2038 and ML0286).The majority of amino acid residues were observed in favorable and allowed regions in the Ramachandran plot,indicating correct positioning of the side chain and absence of steric impediment.The MolProbity score value and Verify 3D results of all models indicated a satisfactory prediction.CONCLUSION The polarized immune response against M.leprae creates a problem in leprosy detection.The selection of immunodominant epitopes is essential for the development of more sensitive serodiagnostic tests,for this it is important to know the three-dimensional structure of the antigens,which can be predicted with bioinformatics tools.
基金supported by the National Natural Science Foundation of China (No.22176067).
文摘The treatment and disposal of radioactive waste are presently facing great challenges.Spent ion exchange resins have become a focus of attention due to their high production and serious environmental risks.In this paper,a simplified model of cationic exchange resin is proposed,and the degradation processes of cationic resin monomer initiated by hydroxyl radicals(·OH)are clarified by combining statistical molecular fragmentation(SMF)model and density functional theory(DFT)calculations.The prediction of active sites indicates that the S-O bonds and the C-S bond of the sulfonic group are more likely to react during the degradation.The meta-position of the sulfonic group on the benzene ring is the most active site,and the benzene ring without the sulfonic group has a certain reactivity.The C11-C14 and C17-C20 bonds,on the carbon skeleton,are the most easily broken.It is also found that dihydroxy addition and elimination reactions play a major role in the process of desulfonation,carbon skeleton cleavage and benzene ring separation.The decomposition mechanisms found through the combination of physical models and chemical calculations,provide theoretical guidance for the treatment of complex polycyclic aromatic hydrocarbons.
基金supported by Natural Science Founda tion of Ningxia(No.2020AAC03018)financial supports from Key R&D Projects of Ningxia(No.2018BCE01002)National Academic Subjects Construction Project of Ningxia(Chemical Engineering and Technology,NXYLXK2017A04)。
文摘Understanding and modulating the interaction between various reactive molecules and oxygen carriers are the key issue to achieve process intensification of chemical looping technology.C1 chemical molecules play an important role in many reactions involved with chemical looping processes.However,up to now,there is still a lack of systematic and in-depth understanding of the adsorption mechanism of C1 molecules on the surface of oxygen carriers(OCs).In this work,the intrinsic interaction between a series of C1 molecules composed of CH4,CO,CO2,CH3OH,HCHO and HCOOH and surface of Ni O OCs in the chemical looping process have been studied using density functional theory calculations.Various adsorption configurations of C1 molecules and also different adsorption sites of Ni O have been considered.The structural features of stable configuration of C1 molecules on the surface of NiO OCs have been obtained.Further,the interacted sites,types and strengths of C1 molecules on the surface of NiO have been directly pictured by the independent gradient model methods.Also,the nature of the interaction between C1 molecule and Ni O surface has been investigated with the aid of energy decomposition analysis from a quantitative view.
文摘Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin receptors(5-HTRs), which is a promising tool in the determination of the receptor’s function and relationship with the diseases related to serotonin and its receptor dysfunction. Serotonin was effectively labeled via a direct electrophilic substitutional reaction using an oxidizing agent such as iodogen with 125I in a neutral medium, and 125I-serotonin was achieved with a maximum labeling yield of 91 ± 0.63% with in vitro stability up to 24 h. Molecular modeling was conducted to signify 125I-serotonin structure and confirm that the radiolabeling process did not affect serotonin binding ability to its receptors. Biodistribution studies show that the maximum gastro intestinal tract uptake of 125I-serotonin was 17.8 ± 0.93% ID/organ after 30 min postinjection and the tracer’s ability to pass the blood–brain barrier. Thus, 125I-serotonin is a promising single photon emission computed tomography tracer in the detection of 5 HTRs.
文摘Cdc25 phosphatase have been regarded as attractive drug targets for anticancer therapies due to the correlation of their over expression with a wide variety of cancers. They are key regulators of cell cycle progression and play a central role in the checkpoint response to DNA damage. The role of Cdc25 s in cancer has become increasingly evident in recent years. More than 20 studies of patient samples are from diverse cancers show significant overexpression of Cdc25 with frequent correlation to clinical outcome. Recent screening and design efforts have yielded novel classes of inhibitors that show specificity for the Cdc25 s over other phosphatases and cause cell cycle arrest in vivo. Until now, quinone derivatives are among the most efficient inhibitors of Cdc25 phosphatase activity. Our research objective is to study the inhibition of the phosphathase Cdc25 through the molecular modeling methods.
