Thermodynamics calculation of protein- ligand interactions by QM/ MM polarizable charge parameters

doi:10.1080/07391102.2015.1019928

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Thermodynamics calculation of protein- ligand interactions by QM/ MM polarizable charge parameters
	Wang, Jinan 1; Shao, Qiang1 ; Cossins, Benjamin P.2; Shi, Jiye 2; Chen, Kaixian1 ; Zhu, Weiliang1
刊名	JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
	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.
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
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	TAYLOR & FRANCIS INC
WOS记录号	WOS:000368032100013
内容类型	期刊论文
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.