REFINEMENT AND RESCORING THE DOCKING RESULTS

对接结果的细化和重新评分

• 批准号: 8363595
• 负责人: MATTHEW P JACOBSON
• 金额: $ 1.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363595
• 关键词: Affinity; Binding; DHFR gene; Docking; Enzymes; Escherichia coli; Funding; Grant; Imagery; Informatics; Ligands; Methods; National Center for Research Resources; Nature; Principal Investigator; Relative (related person); Research; Research Infrastructure; Resources; Source; United States National Institutes of Health; base; biocomputing; cost; enolase; inhibitor/antagonist; programs; receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have developed a new methodlogy to refine and rescore the docking results. The docking programs use scoring function to determine the relative binding affinity of ligands and rank order them. These scoring functions are often approximate and empirical in nature. We believe that the large number of false positives seen in the docking results are due to the inadequacy in the docking scoring functions. We have developed a method based on all-atom force field with implicit solvation. Our method is quite robust and very fast. For instance it takes only 45 seconds to refine a ligand. We have applied the method to identify putative substrates for enolase superfamily enzymes and also identify inhibitors against E.coli DHFR receptor.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们开发了一种新的方法来改进和重新评分对接结果。 对接程序使用评分函数来确定相对结合 配体的亲和力并对它们进行排序。 这些评分功能通常 近似的和经验性的。 我们认为，对接结果中出现的大量误报是由于对接评分功能的不足。 我们发展了一种基于全原子力场的隐式溶剂化方法。 我们的方法是非常强大和非常快。 例如，它只需要45秒来提炼配体。 我们已经应用该方法来鉴定烯醇化酶超家族酶的推定底物，并且还鉴定针对大肠杆菌DHFR受体的抑制剂。