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2019中国化学会第十五届全国计算（机）化学学术会议

作者：赵丹 Shijun Zhong 大连理工大学 School of Bioengineering Dalian University of Technology

Protein tyrosine phosphatase 1 B（PTP1 B） is considered as a negative regulator of insulin signaling and an important target for the treatment of type II diabetes and obesity. Inhibition of PTP1 B can enhance insulin signaling[1]. A series of varic acid analogues were reported as PTP1 B inhibitors[2]. We investigate the binding modes and inhibition mechanisms of these inhibitors using molecular docking, molecular dynamics simulations and MM/GBSA binding free energy decomposition analysis. After re-docking validation of three docking programs（Auto Dock Vina[3], LeDock[4] and DOCK[5]）, the binding poses of AutoDock Vina and LeDock programs were selected as the initial conformations of subsequent MD simulation. Based on the binding free energy of MM/GBSA, the most favorable binding mode of each inhibitor was determined. According to the results of multi-copy binding free energy, the rank of calculated binding free energies（ΔGbind） of these inhibitors is in excellent agreement with that of experimental bioactivity data（IC50）. The correlation coefficient between the MM/GBSA results and experimental binding data was 0.95. The electrostatic energy is dominated component of the total energy. Although these six compounds have similar chemical structures, their binding modes and binding mechanisms are different. The monocyclic molecules（compound 1-3） have significant interactions with residues from Cys215 to Arg221. The bicyclic molecules（compound 4-5） can form hydrogen bonds with ASP48 or Glu115. The tricyclic molecule（compound 6） shows strongest binding affinity because it occupies both the active site（P loop） and the secondary binding site. Based on the structure of compound 6, 17 derivatives were designed and calculated using molecular docking and MD simulation. Among them, 8 derivatives have stronger binding ability with PTP1 B and can be suggested as the varic acid inhibitors for experimental validation.

关键词： PTP1B inhibitors binding modes molecular docking molecular dynamics simulation binding free energy

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An empirical molecular docking study of a di-iron binding protein with iron ions

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Journal of Zhejiang University-Science C(Computers and Electronics) 2013年第2期14卷 118-124页

作者： Huan WANG Ping LIU Hao XIE School of Computer Science and Technology Wuhan University of Technology Institute of Sciences Wuhan University of Technology School of Information Management Wuhan University

Various molecular docking software packages are available for modeling interactions between small molecules and ***,there have been few reports of modeling the interactions between metal ions and *** this study,the AutoDock package was employed to example docking into a di-iron binding protein,*** binding site of this protein was tested for docking with iron *** docking experiments showed that all docking conformations converged into two clusters,one for internal iron binding in sites within the metalloprotein and the other for external iron binding on the protein *** docking experiments showed that there were significant differences between two internal iron binding *** at one site gave a reasonable root-mean-square deviation(RMSD) distribution with relatively low binding *** of the binding mode quality for this site revealed that more than half of the docking conformations were categorized as having good binding geometry,while no good conformations were found for the other *** investigations indicated that coordinating water molecules contributed to the stability of binding *** study provides an empirical approach towards the study of molecular docking in metalloproteins.

关键词： AutoDock Docking Iron ions Metalloproteins binding modes

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维普期刊数据库

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Mechanism of inhibitor ADS-J1 and ADS-J2 binding to HIV-1 gp41

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Journal of Southeast University(English Edition) 2011年第3期27卷 280-283页

作者：宋坤忠孙岳明东南大学化学化工学院南京211189

In order to analyze and explain the mechanism of the two small inhibitors （ADS-JI and ADS-J2） binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these compounds onto the hydrophobic pocket on gp41 and characterize structures of binding complexes. The binding interactions of gp41-molecule and free energies of binding are obtained through molecular dynamics simulation and molecular mechanic/Poisson- Boitzmann surface area （ MM/PBSA ） calculation. Specific molecular interactions in the gp41-inhibitor complexes are identified. The present computational study complements the corresponding experimental investigation and helps establish a good starting point tbr further refinement of small molecular gp41 inhibitors.

关键词： HIV-1 entry inhibitor binding modes gp41 binding free energy

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维普期刊数据库

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Synthesis and the anti-HIV activity of novel dinucleotides containing L-isonucleosides

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Journal of Chinese Pharmaceutical Sciences 2013年第4期22卷 314-318页

作者：王萌邢磊陆世芳关注杨振军张礼和北京大学医学部天然药物及仿生药物国家重点实验室药学院药物化学系北京100191

Three dinucleotides containing L-isonucleosides at 5＇-end were synthesized by an elegant phosphoramidite one-pot method. Their binding modes with HIV integrase were simulated and their anti-HIV activities in pseudoty... 详细信息

关键词： HIV integrase Dinucleotides Synthesis Anti-HIV binding modes

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