Computational Feasibility of an Exhaustive Search of Side-Chain Conformations in Protein-Protein Docking,Journal of Computational Chemistry

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Computational Feasibility of an Exhaustive Search of Side-Chain Conformations in Protein-Protein Docking
Journal of Computational Chemistry ( IF 3.4 ) Pub Date : 2018-09-15 , DOI: 10.1002/jcc.25381
Taras Dauzhenka ₁ , Petras J. Kundrotas ₁ , Ilya A. Vakser _{1,

2}

Affiliation

Protein‐protein docking procedures typically perform the global scan of the proteins relative positions, followed by the local refinement of the putative matches. Because of the size of the search space, the global scan is usually implemented as rigid‐body search, using computationally inexpensive intermolecular energy approximations. An adequate refinement has to take into account structural flexibility. Since the refinement performs conformational search of the interacting proteins, it is extremely computationally challenging, given the enormous amount of the internal degrees of freedom. Different approaches limit the search space by restricting the search to the side chains, rotameric states, coarse‐grained structure representation, principal normal modes, and so on. Still, even with the approximations, the refinement presents an extreme computational challenge due to the very large number of the remaining degrees of freedom. Given the complexity of the search space, the advantage of the exhaustive search is obvious. The obstacle to such search is computational feasibility. However, the growing computational power of modern computers, especially due to the increasing utilization of Graphics Processing Unit (GPU) with large amount of specialized computing cores, extends the ranges of applicability of the brute‐force search methods. This proof‐of‐concept study demonstrates computational feasibility of an exhaustive search of side‐chain conformations in protein pocking. The procedure, implemented on the GPU architecture, was used to generate the optimal conformations in a large representative set of protein‐protein complexes. © 2018 Wiley Periodicals, Inc.

中文翻译：

在蛋白质-蛋白质对接中详尽搜索侧链构象的计算可行性

蛋白质-蛋白质对接程序通常执行蛋白质相对位置的全局扫描，然后是推定匹配的局部细化。由于搜索空间的大小，全局扫描通常作为刚体搜索实现，使用计算成本低的分子间能量近似值。适当的改进必须考虑到结构的灵活性。由于细化对相互作用的蛋白质进行构象搜索，考虑到大量的内部自由度，它在计算上极具挑战性。不同的方法通过将搜索限制在侧链、旋转异构状态、粗粒度结构表示、主要正常模式等来限制搜索空间。尽管如此，即使有近似值，由于剩余自由度的数量非常多，改进提出了一个极端的计算挑战。鉴于搜索空间的复杂性，穷举搜索的优势是显而易见的。这种搜索的障碍是计算可行性。然而，现代计算机不断增长的计算能力，特别是由于具有大量专用计算核心的图形处理单元 (GPU) 的利用率不断提高，扩展了蛮力搜索方法的适用范围。这项概念验证研究证明了在蛋白质麻疹中详尽搜索侧链构象的计算可行性。该程序在 GPU 架构上实施，用于在大量具有代表性的蛋白质-蛋白质复合物中生成最佳构象。

更新日期：2018-09-15

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