Maximal Unbiased Benchmarking Data Sets for Human Chemokine Receptors and Comparative Analysis.
Maximal Unbiased Benchmarking Data Sets for Human Chemokine Receptors and Comparative Analysis.
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DOI：
10.1021/acs.jcim.8b00004
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发表时间：
2018-05-29
影响因子：
5.6
通讯作者：
Wang XS
中科院分区：
文献类型：
--
作者：
Xia J;Reid TE;Wu S;Zhang L;Wang XS
趋化因子受体（Chemokine receptor，CRs）一直是治疗炎症性疾病和HIV 1感染的药物靶点.虚拟筛选作为一种强有力的技术，已被广泛应用于识别包括CR在内的现代药物靶点的小分子先导化合物。为了合理选择各种VS方法，基于基准数据集的配体富集评估已成为不可或缺的实践。然而，缺乏用于整个CR家族的能够无偏地评估每一种方法（包括基于结构和配体的VS）的通用基准集，这在一定程度上阻碍了现代药物发现工作。为了解决这个问题，我们使用我们最近开发的MUBD-DecoyMaker工具构建了人类趋化因子受体（MUBD-hCR）的最大无偏基准数据集。MUBD-hCRs包括20种趋化因子受体中的13种亚型，迄今为止由404种配体和15756种诱饵组成，并且在未来易于扩展。已经彻底验证了MUBD-hCR配体是化学多样性的，而其诱饵在“人工富集”、“类似物偏倚”方面是最大无偏倚的。此外，我们研究了MUBD-hCR的性能，特别是CXCR 4和CCR 5数据集，在基于结构和配体的VS方法的配体富集评估中，与公共领域中可用的其他基准数据集进行比较，并证明MUBD-hCR非常能够指定最佳VS方法。总的来说，MUBD-hCR是一个独特的、最大限度无偏的基准测试集，涵盖了迄今为止的主要CR亚型。
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.
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影响因子：
56.9
作者：
Feng, Y;Broder, CC;Berger, EA
通讯作者：
Berger, EA
影响因子：
5.6
作者：
Gatica, Edgar A.;Cavasotto, Claudio N.
通讯作者：
Cavasotto, Claudio N.
影响因子：
64.8
作者：
Deng, HK;Liu, R;Landau, NR
通讯作者：
Landau, NR
DOI：
10.1007/978-1-60761-839-3_11
发表时间：
2011-01-01
期刊：
CHEMOINFORMATICS AND COMPUTATIONAL CHEMICAL BIOLOGY
影响因子：
--
作者：
Horvath, Dragos
通讯作者：
Horvath, Dragos
影响因子：
7.3
作者：
Bissantz, C;Folkers, G;Rognan, D
通讯作者：
Rognan, D