Accurate prediction of relative binding affinities of a series of HIV-1 protease inhibitors using semi-empirical quantum mechanical charge

doi:10.1002/jcc.26218

	Accurate prediction of relative binding affinities of a series of HIV-1 protease inhibitors using semi-empirical quantum mechanical charge
	Peng, Cheng 1,2,3; Wang, Jinan 1,2; Xu, Zhijian 1,2,3; Cai, Tingting 1,2; Zhu, Weiliang 1,2,3,4
刊名	JOURNAL OF COMPUTATIONAL CHEMISTRY
	2020-04-30
页码	8
关键词	adaptive steered molecular dynamics (ASMD) binding affinity HIV-1 protease semi-empirical quantum mechanics
ISSN号	0192-8651
DOI	10.1002/jcc.26218
通讯作者	Zhu, Weiliang(wlzhu@simm.ac.cn)
英文摘要	A major challenge in computer-aided drug design is the accurate estimation of ligand binding affinity. Here, a new approach that combines the adaptive steered molecular dynamics (ASMD) and partial atomic charges calculated by semi-empirical quantum mechanics (SQMPC), namely ASMD-SQMPC, is suggested to predict the ligand binding affinities, with 24 HIV-1 protease inhibitors as testing examples. In the ASMD-SQMPC, the relative binding free energy (Delta G) is reflected by the average maximum potential of mean force ((max)) between bound and unbound states. The correlation coefficient (R-2) between the (max) and experimentally determined Delta G is 0.86, showing a significant improvement compared with the conventional ASMD (R-2 = 0.52). Therefore, this study provides an efficient approach to predict the relative Delta G and reveals the significance of precise partial atomic charges in the theoretical simulations.
资助项目	National Key Research and Development Program[2016YFA0502301] ; National Natural Science Foundation of China[81573350] ; National Natural Science Foundation of China[81872797] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program[2018ZX09711002]
WOS关键词	FREE-ENERGY CALCULATIONS ; DRUG-RESISTANT MUTANTS ; STRUCTURE-BASED DESIGN ; MOLECULAR-DYNAMICS ; WILD-TYPE ; POTENT ; OPTIMIZATION ; DISCOVERY ; CHEMISTRY ; IMPROVE
WOS研究方向	Chemistry
语种	英语
出版者	WILEY
WOS记录号	WOS:000529628200001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280501]
专题	中国科学院上海药物研究所
通讯作者	Zhu, Weiliang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, 555 Zuchongzhi Rd, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing, Peoples R China 4.Pilot Natl Lab Marine Sci & Technol Qingdao, Open Studio Druggabil Res Marine Nat Prod, 1 Wenhai Rd, Qingdao, Peoples R China
推荐引用方式 GB/T 7714	Peng, Cheng,Wang, Jinan,Xu, Zhijian,et al. Accurate prediction of relative binding affinities of a series of HIV-1 protease inhibitors using semi-empirical quantum mechanical charge[J]. JOURNAL OF COMPUTATIONAL CHEMISTRY,2020:8.
APA	Peng, Cheng,Wang, Jinan,Xu, Zhijian,Cai, Tingting,&Zhu, Weiliang.(2020).Accurate prediction of relative binding affinities of a series of HIV-1 protease inhibitors using semi-empirical quantum mechanical charge.JOURNAL OF COMPUTATIONAL CHEMISTRY,8.
MLA	Peng, Cheng,et al."Accurate prediction of relative binding affinities of a series of HIV-1 protease inhibitors using semi-empirical quantum mechanical charge".JOURNAL OF COMPUTATIONAL CHEMISTRY (2020):8.