Our work shows that differdnt compound orientations have different results in Comparative Molecular Field Analysis(CoMFA).For three analyzed compound series,the squared correlation coefficients of cross-validation(q2)...Our work shows that differdnt compound orientations have different results in Comparative Molecular Field Analysis(CoMFA).For three analyzed compound series,the squared correlation coefficients of cross-validation(q2)could vary as largely as 0.30～0.40 among all possible orientations.THe reason for this comes from the routine adopted by CoMFA which uses discrete,regularly arrayed grids to represent the molecular field.Therefore,different orientatins may map their molecular fields differently onto the grid and accordingly give different results from partial least square(PLS)analyses.We have developed a method all-orientation searching,to seek for the orientation with the best CoMFA result. And ,we suggest that all-orietnation searching shoule be incorporated intto the standard CoMFA procedurd.展开更多
A new lnethod is presented for the calculation of octanol/water partition coefficients.On the basis of summation of atomic contributions, our algorithm, namely;XLOGP, also incorporate correction factors into the calcu...A new lnethod is presented for the calculation of octanol/water partition coefficients.On the basis of summation of atomic contributions, our algorithm, namely;XLOGP, also incorporate correction factors into the calculation. Multivarlate regression aIlalysis was performed on a traming database of 1831 organic compounds with diverse structures to give the final model. The correlation coefficients for the whole set fitting is 0.968 and the standard deviation is O.37. The result sllows that our model is accturate enough for logP estmimation in QSAR studies. Compared to other similar approashes, our method gives better results and is more convenient to use.展开更多
logP is an importat paramter for evaluating the hydrophobicity of organic compounds and other species. It is widely used in 2D-QSAR and recently in 3D-QSAR studies. On the basis of the current fragment addition method...logP is an importat paramter for evaluating the hydrophobicity of organic compounds and other species. It is widely used in 2D-QSAR and recently in 3D-QSAR studies. On the basis of the current fragment addition method, we proposed a new algo rithm called XLOGP by introducing atomic paramters like atom accessible surfaces, van der Waals volums and partial charges. Step-wise multiple regression on a test set of 400 orgtanic compounds were carried out. The model was then tested by cross-validation. The final correlation coefficient for the whole data set fitting and for cross -validation is 0.982 and 0.971, respectively. This shows that the model obtained is valid both at data fitting and at prediction. Compared to other algorithm, this method can discriminate a common atom or fragment in different environment.展开更多
Based on amino acid addition model, a set of hydrophobicity contributions of amino acids was obtained from the multivariate linear regression analysis of peptides’ octanol/water partition coefficients. Multivedate re...Based on amino acid addition model, a set of hydrophobicity contributions of amino acids was obtained from the multivariate linear regression analysis of peptides’ octanol/water partition coefficients. Multivedate regression was performed on a training set of 219 peptides including dipeptides to pentapephdes which we compose 21 natural andno acids. The correlation coefficients for the whole set fitting are 0. 978 and 0- 974, for log P and log D respectively. In addition, a new test method -evolution test-for regression analysis was discussed. The result of evoluhon test for amino acid addition model shows the advantage of this new test method.展开更多
定量计算药物-靶标亲合性一直是分子靶向药物设计中的核心问题之一.亲合性打分函数适用范围宽、计算速度快且精度良好,特别适合与分子对接等方法联用,在药物研发中得到了广泛的应用.经过20多年的发展,目前存在数量繁多的打分函数,这些...定量计算药物-靶标亲合性一直是分子靶向药物设计中的核心问题之一.亲合性打分函数适用范围宽、计算速度快且精度良好,特别适合与分子对接等方法联用,在药物研发中得到了广泛的应用.经过20多年的发展,目前存在数量繁多的打分函数,这些方法难免良莠不齐.建立客观公正的针对打分函数性能的评价体系,不仅可以帮助用户做出合理的选择,也为发展打分函数的理论研究人员提供依据,因此是打分函数研究领域中的一个基础问题.近年来,我们逐步发展了评价药物-靶标亲合性打分函数性能的方法体系(comparative assessment of scoring functions,CASF),为解决该问题提供了一种可行的方案.我们提出了一整套衡量打分函数性能的基本指标,为每种指标设计了相应的定量方法,并确立了将打分过程与构象采样过程分开处理的原则.我们的方法体系中所使用的测试集,源自对PDBbind-CN数据库中蛋白-配体复合物样本的层层筛选,质量较高并且具备结构多样性的特点.与前人的类似工作相比,我们的方法体系具有较强的系统性和先进性,受到了国内外同行的广泛认可和应用.本文介绍了我们建立的CASF方法体系的设计思想、获得的重要研究成果以及学术影响.展开更多
文摘Our work shows that differdnt compound orientations have different results in Comparative Molecular Field Analysis(CoMFA).For three analyzed compound series,the squared correlation coefficients of cross-validation(q2)could vary as largely as 0.30～0.40 among all possible orientations.THe reason for this comes from the routine adopted by CoMFA which uses discrete,regularly arrayed grids to represent the molecular field.Therefore,different orientatins may map their molecular fields differently onto the grid and accordingly give different results from partial least square(PLS)analyses.We have developed a method all-orientation searching,to seek for the orientation with the best CoMFA result. And ,we suggest that all-orietnation searching shoule be incorporated intto the standard CoMFA procedurd.
文摘A new lnethod is presented for the calculation of octanol/water partition coefficients.On the basis of summation of atomic contributions, our algorithm, namely;XLOGP, also incorporate correction factors into the calculation. Multivarlate regression aIlalysis was performed on a traming database of 1831 organic compounds with diverse structures to give the final model. The correlation coefficients for the whole set fitting is 0.968 and the standard deviation is O.37. The result sllows that our model is accturate enough for logP estmimation in QSAR studies. Compared to other similar approashes, our method gives better results and is more convenient to use.
文摘logP is an importat paramter for evaluating the hydrophobicity of organic compounds and other species. It is widely used in 2D-QSAR and recently in 3D-QSAR studies. On the basis of the current fragment addition method, we proposed a new algo rithm called XLOGP by introducing atomic paramters like atom accessible surfaces, van der Waals volums and partial charges. Step-wise multiple regression on a test set of 400 orgtanic compounds were carried out. The model was then tested by cross-validation. The final correlation coefficient for the whole data set fitting and for cross -validation is 0.982 and 0.971, respectively. This shows that the model obtained is valid both at data fitting and at prediction. Compared to other algorithm, this method can discriminate a common atom or fragment in different environment.
文摘Based on amino acid addition model, a set of hydrophobicity contributions of amino acids was obtained from the multivariate linear regression analysis of peptides’ octanol/water partition coefficients. Multivedate regression was performed on a training set of 219 peptides including dipeptides to pentapephdes which we compose 21 natural andno acids. The correlation coefficients for the whole set fitting are 0. 978 and 0- 974, for log P and log D respectively. In addition, a new test method -evolution test-for regression analysis was discussed. The result of evoluhon test for amino acid addition model shows the advantage of this new test method.
基金supported by the National Natural Science Foundation of China(81172984,21072213,21002117,21102168,21102165)National High-Tech Research and Development Program of China(863)(2012AA020308)~~
文摘定量计算药物-靶标亲合性一直是分子靶向药物设计中的核心问题之一.亲合性打分函数适用范围宽、计算速度快且精度良好,特别适合与分子对接等方法联用,在药物研发中得到了广泛的应用.经过20多年的发展,目前存在数量繁多的打分函数,这些方法难免良莠不齐.建立客观公正的针对打分函数性能的评价体系,不仅可以帮助用户做出合理的选择,也为发展打分函数的理论研究人员提供依据,因此是打分函数研究领域中的一个基础问题.近年来,我们逐步发展了评价药物-靶标亲合性打分函数性能的方法体系(comparative assessment of scoring functions,CASF),为解决该问题提供了一种可行的方案.我们提出了一整套衡量打分函数性能的基本指标,为每种指标设计了相应的定量方法,并确立了将打分过程与构象采样过程分开处理的原则.我们的方法体系中所使用的测试集,源自对PDBbind-CN数据库中蛋白-配体复合物样本的层层筛选,质量较高并且具备结构多样性的特点.与前人的类似工作相比,我们的方法体系具有较强的系统性和先进性,受到了国内外同行的广泛认可和应用.本文介绍了我们建立的CASF方法体系的设计思想、获得的重要研究成果以及学术影响.
