Thermodynamics calculation of protein- ligand interactions by QM/ MM polarizable charge parameters
文献类型：期刊论文
| 作者 | Wang, Jinan1; Shao, Qiang1 ; Cossins, Benjamin P.2; Shi, Jiye2; Chen, Kaixian1; Zhu, Weiliang1
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| 刊名 | JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
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| 出版日期 | 2016 |
| 卷号 | 34期号:1页码:163-176 |
| 关键词 | QM/MM binding free energy calculation MM/GBSA calculation electrostatic interaction drug design |
| ISSN号 | 0739-1102 |
| DOI | 10.1080/07391102.2015.1019928 |
| 文献子类 | Article |
| 英文摘要 | The calculation of protein-ligand binding free energy (G) is of great importance for virtual screening and drug design. Molecular dynamics (MD) simulation has been an attractive tool to investigate this scientific problem. However, the reliability of such approach is affected by many factors including electrostatic interaction calculation. Here, we present a practical protocol using quantum mechanics/molecular mechanics (QM/MM) calculations to generate polarizable QM protein charge (QMPC). The calculated QMPC of some atoms in binding pockets was obviously different from that calculated by AMBER ff03, which might significantly affect the calculated G. To evaluate the effect, the MD simulations and MM/GBSA calculation with QMPC for 10 protein-ligand complexes, and the simulation results were then compared to those with the AMBER ff03 force field and experimental results. The correlation coefficient between the calculated G using MM/GBSA under QMPC and the experimental data is .92, while that with AMBER ff03 force field is .47 for the complexes formed by streptavidin or its mutants and biotin. Moreover, the calculated G with QMPC for the complexes formed by ER and five ligands is positively related to experimental result with correlation coefficient of .61, while that with AMBER ff03 charge is negatively related to experimental data with correlation coefficient of .42. The detailed analysis shows that the electrostatic polarization introduced by QMPC affects the electrostatic contribution to the binding affinity and thus, leads to better correlation with experimental data. Therefore, this approach should be useful to virtual screening and drug design. |
| WOS关键词 | STREPTAVIDIN-BIOTIN SYSTEM ; BINDING FREE-ENERGY ; MOLECULAR-DYNAMICS SIMULATIONS ; CONTINUUM SOLVENT MODELS ; FORCE-FIELD ; ELECTROSTATIC POLARIZATION ; RELATIVE AFFINITIES ; HIV-1 PROTEASE ; DIVERSE SET ; COMBINATION |
| 资助项目 | National Natural Science Foundation of China (NNSFC)[21403283] ; National Natural Science Foundation of China (NNSFC)[21373258] ; National Natural Science Foundation of China (NNSFC)[21021063] ; National Natural Science Foundation of China (NNSFC)[81273435] ; Postdoctoral Science Foundation of China[2014M560362] ; National 863 Program[2012AA01A305] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000368032100013 |
| 出版者 | TAYLOR & FRANCIS INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276263]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Shao, Qiang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; 2.UCB Pharma, Dept Informat, Slough SL1 4EN, Berks, England |
| 推荐引用方式 GB/T 7714 | Wang, Jinan,Shao, Qiang,Cossins, Benjamin P.,et al. Thermodynamics calculation of protein- ligand interactions by QM/ MM polarizable charge parameters[J]. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS,2016,34(1):163-176. |
| APA | Wang, Jinan,Shao, Qiang,Cossins, Benjamin P.,Shi, Jiye,Chen, Kaixian,&Zhu, Weiliang.(2016).Thermodynamics calculation of protein- ligand interactions by QM/ MM polarizable charge parameters.JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS,34(1),163-176. |
| MLA | Wang, Jinan,et al."Thermodynamics calculation of protein- ligand interactions by QM/ MM polarizable charge parameters".JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS 34.1(2016):163-176. |
入库方式： OAI收割
来源：上海药物研究所
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