论文标题
耗散校正的靶向分子动力学模拟的蛋白质 - 配体解开的靶向分子动力学模拟的路径分离
Path separation of dissipation-corrected targeted molecular dynamics simulations of protein-ligand unbinding
论文作者
论文摘要
蛋白质 - 配体（UN）结合模拟是偏置分子动力学模拟的最新焦点。这种结合和解开可以通过不同的途径进出结合位点发生。在这里，我们提出了一个理论框架，如何沿单独的路径计算动力学，并将路径特异性速率结合到与实验进行比较的全局结合率和解开速率中。结合耗散校正的靶向分子动力学与促进温度的Langevin方程模拟结合使用[Nat。社区。 \ textbf {11}，2918（2020）]应用于二维模型和胰蛋白酶 - 苯甲胺岛复合物作为测试系统，我们评估了程序的鲁棒性，并讨论了其实际适用性，以预测复杂生物分子系统的多秒动力学。
Protein-ligand (un)binding simulations are a recent focus of biased molecular dynamics simulations. Such binding and unbinding can occur via different pathways in and out of a binding site. We here present a theoretical framework how to compute kinetics along separate paths and to combine the path-specific rates into global binding and unbinding rates for comparison with experiment. Using dissipation-corrected targeted molecular dynamics in combination with temperature-boosted Langevin equation simulations [Nat. Commun. \textbf{11}, 2918 (2020)] applied to a two-dimensional model and the trypsin-benzamidine complex as test systems, we assess the robustness of the procedure and discuss aspects of its practical applicability to predict multisecond kinetics of complex biomolecular systems.
