REFINEMENT AND RESCORING THE DOCKING RESULTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们已经开发了一种新的方法来提炼和重新计算对接结果。 对接程序使用评分函数来确定相对绑定 配基的亲和力和排列顺序。这些计分函数通常是 近似性的和经验性的。我们认为，对接结果出现大量假阳性是由于对接计分功能不足。我们发展了一种基于全原子力场的隐式求解方法。我们的方法非常健壮，而且速度非常快。例如，提纯一个配体只需要45秒。我们已将该方法应用于鉴定烯醇化酶超家族酶的可能底物，并鉴定了针对E.ColiDHFR受体的抑制剂。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.