The Impact of Side-Chain Packing on Protein Docking Refinement
The Impact of Side-Chain Packing on Protein Docking Refinement
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DOI：
10.1021/ci500380a
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发表时间：
2015-04-01
影响因子：
5.6
通讯作者：
Kozakov, Dima
中科院分区：
文献类型：
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作者：
Moghadasi, Mohammad;Mirzaei, Hanieh;Kozakov, Dima
我们研究了在结合过程中优化两种蛋白质之间界面区域侧链位置的影响。从数学上讲，该问题类似于侧链预测，在蛋白质结构预测过程中已被广泛探索。然而，蛋白质-蛋白质对接应用程序具有许多特征，需要不同的算法和实现选择。在这项工作中，我们实现了一种分布式近似算法，该算法可以在多处理器架构上实现，并可以在精度和运行速度之间进行权衡。我们报告了酶抑制剂和其他类型复合物基准的计算结果，证明我们的算法引入的侧链灵活性大大提高了对接协议的性能。此外，我们确定在侧链定位问题中包含未结合的侧链构象异构体对于这些性能改进至关重要。该代码可在开源许可下向社区提供。
We study the impact of optimizing the side-chain positions in the interface region between two proteins during the process of binding. Mathematically, the problem is similar to side-chain prediction, which has been extensively explored in the process of protein structure prediction. The protein-protein docking application, however, has a number of characteristics that necessitate different algorithmic and implementation choices. In this work, we implement a distributed approximate algorithm that can be implemented on multiprocessor architectures and enables a trade-off between accuracy and running speed. We report computational results on benchmarks of enzyme-inhibitor and other types of complexes, establishing that the side-chain flexibility our algorithm introduces substantially improves the performance of docking protocols. Furthermore, we establish that the inclusion of unbound side-chain conformers in the side-chain positioning problem is critical in these performance improvements. The code is available to the community under open source license.