普林斯顿TIGRESS:使用模拟和支持向量机进行蛋白质几何结构优化。

Princeton_TIGRESS: protein geometry refinement using simulations and support vector machines.

作者信息

Khoury George A, Tamamis Phanourios, Pinnaduwage Neesha, Smadbeck James, Kieslich Chris A, Floudas Christodoulos A

机构信息

Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey, 08540.

出版信息

Proteins. 2014 May;82(5):794-814. doi: 10.1002/prot.24459. Epub 2013 Nov 22.

Abstract

Protein structure refinement aims to perform a set of operations given a predicted structure to improve model quality and accuracy with respect to the native in a blind fashion. Despite the numerous computational approaches to the protein refinement problem reported in the previous three CASPs, an overwhelming majority of methods degrade models rather than improve them. We initially developed a method tested using blind predictions during CASP10 which was officially ranked in 5th place among all methods in the refinement category. Here, we present Princeton_TIGRESS, which when benchmarked on all CASP 7,8,9, and 10 refinement targets, simultaneously increased GDT_TS 76% of the time with an average improvement of 0.83 GDT_TS points per structure. The method was additionally benchmarked on models produced by top performing three-dimensional structure prediction servers during CASP10. The robustness of the Princeton_TIGRESS protocol was also tested for different random seeds. We make the Princeton_TIGRESS refinement protocol freely available as a web server at http://atlas.princeton.edu/refinement. Using this protocol, one can consistently refine a prediction to help bridge the gap between a predicted structure and the actual native structure.

摘要

蛋白质结构优化旨在针对给定的预测结构执行一系列操作,以盲目方式提高模型相对于天然结构的质量和准确性。尽管在前三次蛋白质结构预测关键评估(CASP)中报道了众多针对蛋白质优化问题的计算方法,但绝大多数方法都会使模型质量下降而非提高。我们最初开发了一种在CASP10期间使用盲目预测进行测试的方法,该方法在优化类别中所有方法中官方排名第5。在此,我们展示了普林斯顿TIGRESS方法,当在所有CASP 7、8、9和10的优化目标上进行基准测试时,该方法在76%的情况下同时提高了全局距离测试总分(GDT_TS),每个结构平均提高0.83个GDT_TS点。该方法还在CASP10期间由表现最佳的三维结构预测服务器生成的模型上进行了基准测试。普林斯顿TIGRESS协议的稳健性也针对不同的随机种子进行了测试。我们将普林斯顿TIGRESS优化协议作为网络服务器免费提供,网址为http://atlas.princeton.edu/refinement。使用此协议,人们可以持续优化预测结果,以帮助弥合预测结构与实际天然结构之间的差距。

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