生物分子构象研究的并行回火算法

Combining Enhanced Sampling with Experiment Directed Simulation of the GYG peptide

Experiment directed simulation is a technique to minimally bias molecular dynamics simulations to match experimentally observed results. The method improves accuracy but does not address the sampling problem of molecular dynamics simulations of large systems. This work combines experiment directed simulation with both the parallel-tempering and parallel-tempering well-tempered ensemble replica-exchange methods to enhance sampling of experiment directed simulations. These methods are demonstrated on the GYG tripeptide in explicit water. The collective variables biased by experiment directed sim…

电磁波与蛋白质构象动力学的共振耦合：通过分子动力学模拟揭示

Resonant Coupling Between Electromagnetic Waves and Protein Conformational Dynamics Revealed by Molecular Dynamics Simulations

通过分子动力学模拟揭示电磁波与蛋白质构象动力学的共振耦合机制，展示共振激发对蛋白质构象的影响。

Exploring RNA structure and dynamics through enhanced sampling simulations

RNA function is intimately related to its structural dynamics. Molecular dynamics simulations are useful for exploring biomolecular flexibility but are severely limited by the accessible timescale. Enhanced sampling methods allow this timescale to be effectively extended in order to probe biologically-relevant conformational changes and chemical reactions. Here, we review the role of enhanced sampling techniques in the study of RNA systems. We discuss the challenges and promises associated with the application of these methods to force-field validation, exploration of conformational landscapes…

增强的采样算法

Enhanced Sampling Algorithms

在具有多自由度的生物分子系统（特别是全原子模型）中，如蛋白质和核酸，存在大量的局域最低能态。在正则系综中的常规模拟几乎没有用处，因为它们往往会被困在这些能量局部最小值的状态中。因此，对增强型构象取样技术的需求很大。广义系综模拟在势能空间中进行随机游走，可以克服这一困难。通过单直方图和/或多直方图重新加权技术，仅从一次模拟运行，就可以获得作为温度的函数的物理量的正则系综平均值。本文综述了广义系综算法在生物分子系统中的应用。三个著名的方法，即多规范算法，模拟回火，复制交换方法，首先进行了描述。Monte Carlo和分子动力学版本的算法。然后，我们提出了这三个广义集成算法的各种扩展。短肽和蛋白质系统的方法的有效性进行了测试。

多结构域蛋白质构象动力学中记忆的无模型推断

Model-free inference of memory in conformational dynamics of a multi-domain protein

本文结合Hsp90单分子等离子体标尺实验、模拟与理论，提出无模型方法推断蛋白质构象动力学中的记忆，发现马尔可夫假设在约50秒时间尺度上被明确违背，并给出检验记忆存在性与持续时间的可重复指导。

使用随机滴定恒pH元动力学模拟表征RNA寡聚体

Characterizing RNA oligomers using Stochastic Titration Constant-pH Metadynamics simulations

本研究将随机滴定恒pH元动力学方法扩展至RNA，结合AMBER力场和PLUMED实现，成功模拟单链RNA核苷酸滴定，pKa预测与实验一致，为研究pH调控RNA结构提供了可靠工具。

Non-covalent interactions across organic and biological subsets of chemical space: Physics-based potentials parametrized from machine learning

Classical intermolecular potentials typically require an extensive parametrization procedure for any new compound considered. To do away with prior parametrization, we propose a combination of physics-based potentials with machine learning (ML), coined IPML, which is transferable across small neutral organic and biologically-relevant molecules. ML models provide on-the-fly predictions for environment-dependent local atomic properties: electrostatic multipole coefficients (significant error reduction compared to previously reported), the population and decay rate of valence atomic densities, an…

利用sketch-map探究β-发夹的去折叠构象

Probing the unfolded configurations of a $β$-hairpin using sketch-map

本研究利用sketch-map算法结合副本交换元动力学模拟分析β-发夹折叠构象系综，发现突变体与野生型存在诸多相同构象，验证了机器学习在复杂分子能量面研究中的应用价值。

Aurora-A激酶的MTSL自旋标记激活环的结构和动力学的MD和EPR研究

MD and EPR studies of the structure and dynamics of the MTSL spin-labelled activation loop of the Aurora-A kinase

对激酶结构的理解主要基于蛋白质晶体学，这受到将分子捕获在晶格内的要求的限制。因此，表征溶液中激活环的构象动力学对于增强对与疾病相关的分子过程的理解和支持小分子激酶抑制剂的发现是重要的。在这项工作中，我们证明了长分子动力学模拟详尽地采样的极光-A激酶和甲烷-硫代磺酸盐自旋标记的激活环的所有构象空间，引入到激活环的电子顺磁测量。MD被用来确定结构波动，序参量和旋转相关时间的激活环和MTSL的运动。所获得的理论数据被用作输入计算的室温9 GHz的连续波EPR的极光-A激酶在溶液中，模拟和实验数据之间的比较显示，运动的蛋白质和自旋标记发生在可比的时间尺度。这项工作是一个起点，更深入的实验和理论研究的旋转和平移扩散特性的极光-A激酶蛋白质相关的生物活性。