Sanchez-Martinez Melchor, Field Martin, Crehuet Ramon
Institute of Advanced Chemistry of Catalonia (IQAC), CSIC , Jordi Girona 18-26, 08034, Barcelona, Spain.
J Phys Chem B. 2015 Jan 22;119(3):1103-13. doi: 10.1021/jp506593t. Epub 2014 Oct 17.
The development of approaches for simulating rare events in complex molecular systems is a central concern in chemical physics. In recent work, Roux and co-workers proposed a novel, swarms of trajectories (SoT) method for determining the transition paths of such events. It consists of the dynamical refinement on the system's free energy surface of a putative transition path that is parametrized in terms of a set of collective variables (CVs) that are identified as being important for the transition. In this work, we have implemented the SoT method and used it to investigate the catalytic mechanisms of two enzymatic reactions using hybrid QM/MM potentials. Our aim has been to test the performance of SoT for enzyme systems and to devise robust simulation protocols that can be employed in future studies of this type. We identify the conditions under which converged results can be obtained using inertial and Brownian dynamical evolutions of the CVs, show that the inclusion of several CVs can give significant additional insight into the mechanisms of the reactions, and show that the use of minimum energy paths as starting guesses can greatly accelerate path refinement.
在复杂分子系统中模拟罕见事件的方法的发展是化学物理领域的核心关注点。在最近的工作中，鲁克斯及其同事提出了一种新颖的轨迹群（SoT）方法，用于确定此类事件的过渡路径。它包括对假定过渡路径在系统自由能面上进行动力学优化，该路径由一组被确定为对过渡至关重要的集体变量（CVs）进行参数化。在这项工作中，我们实现了SoT方法，并使用它结合混合QM/MM势来研究两个酶促反应的催化机制。我们的目标是测试SoT在酶系统中的性能，并设计出可用于未来此类研究的稳健模拟方案。我们确定了使用CVs的惯性和布朗动力学演化能够获得收敛结果的条件，表明纳入多个CVs可以为反应机制提供显著的额外见解，并且表明使用最小能量路径作为初始猜测可以极大地加速路径优化。
