Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations
Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations
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DOI：
10.1016/s0022-2836(03)00670-3
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发表时间：
2003-08-01
影响因子：
5.6
通讯作者：
Baker, D
中科院分区：
文献类型：
--
作者：
Gray, JJ;Moughon, S;Baker, D
蛋白质 - 蛋白质对接算法提供了一种阐明目前未知复合物的结构细节的方法。在这里，我们介绍并评估一种新方法，以预测未结合单体成分坐标的蛋白质蛋白质复合物。该方法采用低分辨率，刚体，蒙特卡洛搜索，然后使用蒙特卡洛最小化对骨干位移和侧链构象进行了同时优化。进行多达10（5）个独立的模拟，并使用由范德华相互作用，隐式溶剂化模型和方向依赖性的氢键势为主导的能量函数对所得的“诱饵”进行排名。顶级诱饵聚集以选择最终预测。小型扰动研究揭示了使用从结合复合物中得出的坐标，在54例中的42例中，使用一个或两个单体的独立确定的坐标，在54例中的42例中形成了结合漏斗。实验结合亲和力与计算的分数函数相关，并解释了许多目标的预测成功或失败。使用一个或两个未结合的组件进行全局搜索预测，在存在结合渠道的32例中，有28个本机残留物残留触点的至少25％。结果表明，该方法可能很快对于从孤立成分的结构中生成生物学上重要的复合物的模型可能很有用，但它们还强调了必须满足的挑战，以实现对蛋白质蛋白质相互作用的一致和准确的预测。 （c）2003 Elsevier Ltd.保留所有权利。
Protein-protein docking algorithms provide a means to elucidate structural details for presently unknown complexes. Here, we present and evaluate a new method to predict protein-protein complexes from the coordinates of the unbound monomer components. The method employs a low-resolution, rigid-body, Monte Carlo search followed by simultaneous optimization of backbone displacement and side-chain conformations using Monte Carlo minimization. Up to 10(5) independent simulations are carried out, and the resulting "decoys" are ranked using an energy function dominated by van der Waals interactions, an implicit solvation model, and an orientation-dependent hydrogen bonding potential. Top-ranking decoys are clustered to select the final predictions. Small-perturbation studies reveal the formation of binding funnels in 42 of 54 cases using coordinates derived from the bound complexes and in 32 of 54 cases using independently determined coordinates of one or both monomers. Experimental binding affinities correlate with the calculated score function and explain the predictive success or failure of many targets. Global searches using one or both unbound components predict at least 25% of the native residue-residue contacts in 28 of the 32 cases where binding funnels exist. The results suggest that the method may soon be useful for generating models of biologically important complexes from the structures of the isolated components, but they also highlight the challenges that must be met to achieve consistent and accurate prediction of protein-protein interactions. (C) 2003 Elsevier Ltd. All rights reserved.