FAST AND SIMPLE MONTE-CARLO ALGORITHM FOR SIDE-CHAIN OPTIMIZATION IN PROTEINS - APPLICATION TO MODEL-BUILDING BY HOMOLOGY
FAST AND SIMPLE MONTE-CARLO ALGORITHM FOR SIDE-CHAIN OPTIMIZATION IN PROTEINS - APPLICATION TO MODEL-BUILDING BY HOMOLOGY
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DOI：
10.1002/prot.340140208
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发表时间：
1992-10-01
期刊：
影响因子：
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通讯作者：
SANDER, C
中科院分区：
文献类型：
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作者：
HOLM, L;SANDER, C
一旦在序列水平上与已知三维结构的蛋白质建立了进化联系，就可以相当准确地预测未知的蛋白质结构。在通过同源性构建模型时，通常从骨架框架开始，重建新的环区域，并替换非保守的侧链。在这里，我们使用一个非常有效的蒙特卡罗算法在旋转异构体空间与模拟退火和简单的势能函数，以优化包装的侧链上给定的骨干模型。优化的模型在几分钟内在工作站上生成，具有合理的准确性（在蛋白质的核心中以优于2.5 A的分辨率确定的平均81%侧链-chi-1二面角正确）。正如预期的那样，模型的质量随着骨架坐标精度的降低而降低。如果骨架取自同源而不是相同的蛋白质，则在强同源性的情况下，约70%的侧链-chi-1角在核心中被正确建模，并且在中等同源性的情况下，约60%的侧链-chi-1角被正确建模。该算法可用于自动化，快速，可重复的同源模型的建立。
An unknown protein structure can be predicted with fair accuracy once an evolutionary connection at the sequence level has been made to a protein of known 3-D structure. In model building by homology, one typically starts with a backbone framework, rebuilds new loop regions, and replaces nonconserved side chains. Here, we use an extremely efficient Monte Carlo algorithm in rotamer space with simulated annealing and simple potential energy functions to optimize the packing of side chains on given backbone models. Optimized models are generated within minutes on a workstation, with reasonable accuracy (average of 81% side chain-chi-1 dihedral angles correct in the cores of proteins determined at better than 2.5 A resolution). As expected, the quality of the models decreases with decreasing accuracy of backbone coordinates. If the backbone was taken from a homologous rather than the same protein, about 70% side chain-chi-1 angles were modeled correctly in the core in a case of strong homology and about 60% in a case of medium homology. The algorithm can be used in automated, fast, and reproducible model building by homology.