标题： 使用集体变量退火的副本交换增强构象采样 显示英文标题

标题： Enhanced Conformational Sampling using Replica Exchange with Collective-Variable Tempering

摘要： 对RNA和蛋白质构象转变的原子分子动力学计算研究通常需要合适的增强采样技术。 我们在此介绍一种新方法，其中同时进行的元动力学被整合到哈密顿量复制交换方案中。 复制体的阶梯是通过不同强度的偏差势能构建的，利用了良好温度元动力学的可调性。 使用此方法，与简单的力场缩放相比，单个集体变量的自由能屏障显著降低。 所引入的方法具有灵活性，并允许为大量简单的集体变量（如距离和二面角）自洽地构建适应性偏差势能。 该方法在丙氨酸二肽上进行了测试，并应用于四核苷酸构象采样的难题。 显示英文摘要

摘要： The computational study of conformational transitions in RNA and proteins with atomistic molecular dynamics often requires suitable enhanced sampling techniques. We here introduce a novel method where concurrent metadynamics are integrated in a Hamiltonian replica-exchange scheme. The ladder of replicas is built with different strength of the bias potential exploiting the tunability of well-tempered metadynamics. Using this method, free-energy barriers of individual collective variables are significantly reduced compared with simple force-field scaling. The introduced methodology is flexible and allows adaptive bias potentials to be self-consistently constructed for a large number of simple collective variables, such as distances and dihedral angles. The method is tested on alanine dipeptide and applied to the difficult problem of conformational sampling in a tetranucleotide.