摘要
以AutoDock 4.2分子对接软件对20种小分子单糖及其类似物与α-葡萄糖苷酶进行分子模拟对接研究,分析对接结合自由能与实验所得IC50的关系,并根据受体与配体的相互作用进一步优化改造抑制剂分子结构。结果显示:α-葡萄糖苷酶分子中氨基酸残基Asp542、Asp443、His600、Asp327和Arg526是化合物与酶形成氢键作用的重要位点。分别将糖环上的O原子替换为N和C原子后,前者的对接结合自由能变得更小,配体与受体结合得更好。对井冈霉胺的分子结构改造后的对接结果显示,六元环上的N原子和环上存在—NH2取代基在分子与α-葡萄糖苷酶对接中起非常重要的作用。本研究可为今后高效α-葡萄糖苷酶抑制剂的筛选和优化设计提供新思路。
The molecular docking study of 20 small-molecule monosaccharides and their analogues withα-glucosidase was carried out with AutoDock 4.2 software.The relationship between the binding free energy and the half-maximum inhibitory concentration(IC50)was analyzed,and the molecular structure of the inhibitor was further optimized according to the interaction between the receptor and the ligand.The results showed that the amino acid residues Asp542,Asp443,His600,Asp327 and Arg526 inα-glucosidase were important sites for hydrogen bonding between each of the compounds and the enzyme.After replacing the O atom on the sugar ring with N or C atoms,the binding free energy of the former became smaller,and the binding of ligand to the receptor was stronger.The docking results after the molecular structure modification of validamine showed that the N atom on the six-membered ring and the presence of the–NH2 substituent on the ring played a very important role in the docking of the molecules withα-glucosidase.This study provides a new idea for the screening and optimized design of high-efficiencyα-glucosidase inhibitors in the future.
作者
徐晓梅
温家颖
王庆华
XU Xiaomei;WEN Jiaying;WANG Qinghua(School of Life Sciences and Biopharmaceuticals,Guangdong Pharmaceutical University,Guangzhou 510006,China;School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,China)
出处
《食品科学》
EI
CAS
CSCD
北大核心
2020年第8期139-143,共5页
Food Science
基金
广东省科技计划项目(2014A020208134)。
关键词
Α-葡萄糖苷酶
抑制剂
分子对接
小分子构建
α-glucosidase
inhibitor
molecular docking
small molecule construction
