Ab initio construction of polypeptide fragments: Accuracy of loop decoy discrimination by an all-atom statistical potential and the AMBER force field with the generalized born solvation model
Ab initio construction of polypeptide fragments: Accuracy of loop decoy discrimination by an all-atom statistical potential and the AMBER force field with the generalized born solvation model
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DOI：
10.1002/prot.10235
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发表时间：
2003-04-01
影响因子：
2.9
通讯作者：
Blundell, TL
中科院分区：
文献类型：
--
作者：
de Bakker, PIW;DePristo, MA;Blundell, TL
通过比较Samudrala-Moult全原子统计势（RAPDF）和AMBER分子力学力场（包括广义Born/表面积溶剂化模型）的性能，探讨了从蛋白质环构象诱饵系综中选择模型的准确性.一致的环构象，表示在原子的细节与理想化的几何形状，大的合奏产生了一个大的测试集的蛋白质环的2至12个残基长的一种新的从头算方法称为RAPPER依赖于细粒度的残留物特定的φ/psi的倾向表的构象采样。基于RAPDF评分对构象异构体进行排序，得到了所选的构象异构体，其对于所有重主链原子具有平均全局非叠加RMSD，范围为4聚体的1.2埃至8聚体的2.9埃至12聚体的6.2埃。在基于锚几何形状和RAPDF分数进行过滤后，通过AMBER/GBSA势能函数的能量最小化进行排序，选择具有对于4聚体为0.5埃、对于8聚体为2.3埃和对于12聚体为5.0埃的全局RMSD值的构象。平均而言，最小化片段的RMSD值始终低于其初始构象（0.1埃）。广义玻恩溶剂化能项的重要性反映在以下观察结果中：当忽略该项时，所有环路长度的平均RMSD精度较差。然而，仍然有许多情况下，AMBER气相最小化选择的构象比AMBER/GBSA最小化的RMSD低。AMBER/GBSA能量函数与RMSD的相关性优于RAPDF。当用从实验结构中提取的构象补充系综时，当用AMBER/GBSA力场评分时，在较长的长度（8聚体的平均RMSD为1.3埃）处观察到选择准确性的显著改善。这项工作提供了一个很有前途的从头算和基于知识的方法回路建模的混合方法的基础。蛋白质2003;51：21-40. (C)2003 Wiley-Liss，Inc.
The accuracy of model selection from decoy ensembles of protein loop conformations was explored by comparing the performance of the Samudrala-Moult all-atom statistical potential (RAPDF) and the AMBER molecular mechanics force field, including the Generalized Born/surface area solvation model. Large ensembles of consistent loop conformations, represented at atomic detail with idealized geometry, were generated for a large test set of protein loops of 2 to 12 residues long by a novel ab initio method called RAPPER that relies on fine-grained residue-specific phi/psi propensity tables for conformational sampling. Ranking the conformers on the basis of RAPDF scores resulted in selected conformers that had an average global, non-superimposed RMSD for all heavy mainchain atoms ranging from 1.2 Angstrom for 4-mers to 2.9 Angstrom for 8-mers to 6.2 Angstrom for 12-mers. After filtering on the basis of anchor geometry and RAPDF scores, ranking by energy minimization of the AMBER/GBSA potential energy function selected conformers that had global RMSD values of 0.5 Angstrom for 4-mers, 2.3 Angstrom for 8-mers, and 5.0 Angstrom for 12-mers. Minimized fragments had, on average, consistently lower RMSD values (by 0.1 Angstrom) than their initial conformations. The importance of the Generalized Born solvation energy term is reflected by the observation that the average RMSD accuracy for all loop lengths was worse when this term is omitted. There are, however, still many cases where the AMBER gas-phase minimization selected conformers of lower RMSD than the AMBER/GBSA minimization. The AMBER/GBSA energy function had better correlation wit RMSD to native than the RAPDF. When the ensembles were supplemented with conformations extracted from experimental structures, a dramatic improvement in selection accuracy was observed at longer lengths (average RMSD of 1.3 Angstrom for 8-mers) when scoring with the AMBER/GBSA force field. This work provides the basis for a promising hybrid approach of ab initio and knowledge-based methods for loop modeling. Proteins 2003;51:21-40. (C) 2003 Wiley-Liss, Inc.