Analysis of trajectories from our rigid-body dynamics simulation package, BioSimz, is used to find regions on the surface of unbound proteins that form frequent and tenacious encounter complexes with their binding partner. Binding partners are significantly more likely to sojourn around true binding regions than around the remainder of the protein surface. This information is used to restrict the search space for flexible protein-protein docking using our SwarmDock algorithm, reducing the computational expense of docking, and improving or matching the ranking of successfully docked poses for all but four of 26 test cases. Running the simulations with external crowder proteins, at near physiological concentration, further enhances the binding region, compared to simulations without external crowders. Information gleaned from these simulations can give mechanistic insights into binding events. The application of these techniques to CAPRI targets 32 and 38-40 is discussed.

译文

:通过我们的刚体动力学仿真程序包BioSimz对轨迹进行分析,可用于发现未结合蛋白表面上与结合伴侣形成频繁且顽强的复合体的区域。结合伴侣比真正的结合区域更可能停留在真正的结合区域附近。该信息用于限制使用我们的SwarmDock算法进行灵活的蛋白质-蛋白质对接的搜索空间,从而减少对接的计算量,并改善或匹配26个测试用例中除四个以外的所有成功对接姿势的排名。与没有外部拥挤物的模拟相比,使用外部拥挤物蛋白质在接近生理浓度的条件下运行模拟可进一步增强结合区域。从这些模拟中收集的信息可以为绑定事件提供机械的见解。讨论了这些技术对CAPRI目标32和38-40的应用。

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