Maximal Unbiased Benchmarking Data Sets for Human Chemokine Receptors and Its Comparative Analysis

摘要：

　　Chemokine receptors(CRs)have long been druggable targets for the treatment of inflammatory diseases and HIV-1 infection.As a powerful technique,virtual screening(VS)has been widely applied to identifying small molecule leads for modern drug targets including CRs.For rational selection of a wide variety of VS approaches,ligand enrichment assessment based on a benchmarking data set has become an indispensable practice.However,the lack of versatile benchmarking sets for the whole CRs family that are able to unbiasedly evaluate every single approaches including both structure-and ligand-based VS,somewhat hinders modern drug discovery efforts.To address this issue,we constructed Maximal-Unbiased Benchmarking Data sets for human Chemokine Receptors(MUBD-hCRs)using our recently developed tools of MUBD-DecoyMaker.The MUBD-hCRs encompasses 13 subtypes out of 20 chemokine receptors,composed of 404 ligands and 15756 decoys so far and are readily expandable in the future.It had been thoroughly validated that MUBD-hCRs ligands are chemically diverse while its decoys are maximal-unbiased in terms of “artificial enrichment”,“analogue bias”.In addition,we studied the performance of MUBD-hCRs,in particular CXCR4 and CCR5 data sets,in ligand enrichment assessments of both structure and ligand-based VS approaches in comparison with other benchmarking data sets available in public domain and demonstrated that MUBD-hCRs is much capable of designating the optimal VS approach.Taken together,MUBD-hCRs is a unique and maximal-unbiased benchmarking set that covers major CRs subtypes so far.

关键词： Chemokine receptor virtual screening ligand enrichment assessment benchmarking data set MUBD-DecoyMaker

作者: Jie Xia Terry-Elinor Reid Song Wu Liangren Zhang Xiang Simon Wang

作者单位: State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Department of New Drug Molecular Modeling and Drug Discovery Core Laboratory for District of Columbia Center for AIDS Resea State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Department of New Drug State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking Univer

会议类型: 国内会议

会议名称: 第九届国际分子模拟与信息技术应用学术会议(ICMS&I2018)

会议地点: 太原

会议语种:英文

页码: 66-118

在线出版日期: 2018-05-01（万方平台首次上网日期，不代表论文的发表时间）