Life Sciences Department, Barcelona Supercomputing Center (BSC), 08034 Barcelona, Spain.
Department of Computer Architecture, Universitat Politècnica de Catalunya, 08034 Barcelona, Spain.
Bioinformatics. 2018 Jan 1;34(1):49-55. doi: 10.1093/bioinformatics/btx555.
Computational prediction of protein-protein complex structure by docking can provide structural and mechanistic insights for protein interactions of biomedical interest. However, current methods struggle with difficult cases, such as those involving flexible proteins, low-affinity complexes or transient interactions. A major challenge is how to efficiently sample the structural and energetic landscape of the association at different resolution levels, given that each scoring function is often highly coupled to a specific type of search method. Thus, new methodologies capable of accommodating multi-scale conformational flexibility and scoring are strongly needed.
We describe here a new multi-scale protein-protein docking methodology, LightDock, capable of accommodating conformational flexibility and a variety of scoring functions at different resolution levels. Implicit use of normal modes during the search and atomic/coarse-grained combined scoring functions yielded improved predictive results with respect to state-of-the-art rigid-body docking, especially in flexible cases.
The source code of the software and installation instructions are available for download at https://life.bsc.es/pid/lightdock/.
Supplementary data are available at Bioinformatics online.
通过对接计算预测蛋白质-蛋白质复合物结构，可以为生物医学感兴趣的蛋白质相互作用提供结构和机制见解。然而，当前的方法在处理困难情况时存在困难，例如涉及柔性蛋白质、低亲和力复合物或瞬时相互作用的情况。主要挑战是如何在不同的分辨率水平上有效地采样关联的结构和能量景观，因为每个评分函数通常与特定类型的搜索方法高度耦合。因此，强烈需要能够适应多尺度构象灵活性和评分的新方法。
我们在这里描述了一种新的多尺度蛋白质-蛋白质对接方法 LightDock，它能够适应构象灵活性和各种评分函数在不同的分辨率水平。在搜索过程中隐式使用模态以及原子/粗粒化的组合评分函数，与最先进的刚体对接相比，特别是在柔性情况下，提高了预测结果。
软件的源代码和安装说明可在 https://life.bsc.es/pid/lightdock/ 下载。
补充数据可在生物信息学在线获得。
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