Prediction of protein side-chain rotamers from a backbone-dependent rotamer library: A new homology modeling tool
Prediction of protein side-chain rotamers from a backbone-dependent rotamer library: A new homology modeling tool
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DOI：
10.1006/jmbi.1997.0926
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发表时间：
1997-04-18
影响因子：
5.6
通讯作者：
Dunbrack, RL
中科院分区：
文献类型：
--
作者：
Bower, MJ;Cohen, FE;Dunbrack, RL
同源建模是将氨基酸序列翻译成蛋白质结构的最准确的计算方法。同源建模可以分为两个子问题，放置多肽骨架和添加侧链。我们提出了一种方法，用于快速预测蛋白质侧链的构象，从主链坐标。该方法涉及使用少于十个旋转异构体，每个残基从主链依赖性旋转异构体库和搜索，以消除空间冲突。该方法最初尝试在299高分辨率晶体结构上重建侧链到实验确定的主链结构上。共有77%的chi（1）和66%的chi（1+2）二面角预测在40度的晶体结构值。然后，我们在蛋白质数据库中已知结构的整个数据库上测试了该方法。该算法的预测精度与结构的分辨率密切相关。为了模拟现实的同源性建模问题，使用三种不同的建模策略创建了9424个同源性模型。为了预测的目的，鉴定了共享30%至90%序列同一性的结构对。一种策略导致82%的chi（1）和72%的chi（1+2）二面角预测在目标晶体结构值的40度内，这表明与这种程度的序列同一性相关的主链的移动不足以破坏我们的方法对非天然主链的预测能力。这些结果与现有的方法相比，在一个全面的数据集。(C)出版社：Academic Press Limited。
Modeling by homology is the most accurate computational method for translating an amino acid sequence into a protein structure. Homology modeling can be divided into two sub-problems, placing the polypeptide backbone and adding side-chains. We present a method for rapidly predicting the conformations of protein side-chains, starting from main-chain coordinates alone. The method involves using fewer than ten rotamers per residue from a backbone-dependent rotamer library and a search to remove steric conflicts. The method is initially tasted on 299 high resolution crystal structures by rebuilding side-chains onto the experimentally determined backbone structures. A total of 77% of chi(1) and 66% of chi(1+2) dihedral angles are predicted within 40 degrees of their crystal structure values. We then tested the method on the entire database of known structures in the Protein Data Bank. The predictive accuracy of the algorithm was strongly correlated with the resolution of the structures. In an effort to simulate a realistic homology modeling problem, 9424 homology models were created using three different modeling strategies. For prediction purposes, pairs of structures were identified which shared between 30% and 90% sequence identity. One strategy results in 82% of chi(1) and 72% chi(1+2) dihedral angles predicted within 40 degrees of the target crystal structure values, suggesting that movements of the backbone associated with this degree of sequence identity are not large enough to disrupt the predictive ability of our method for non-native backbones. These results compared favorably with existing methods over a comprehensive data set. (C) 1997 Academic Press Limited.