【作者】 王晴； 薛托； 宋春年； 王艳； 陈光巨；

【Author】 Qing Wang;Tuo Xue;Chunnian Song;Yan Wang;Guangju Chen;Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education,College of Chemistry, Beijing Normal University;

【机构】 北京师范大学化学学院；

【摘要】 平均力势通常被描述为特定反应坐标的函数,是一种较为准确的自由能计算方法。目前,靶向分子动力学(TMD)模拟和伞状取样(US)方法相结合的方法被应用于丁烷分子的周期性转动以及绒毛蛋白头部域的展开这两种变构过程的平均力势计算当中。基于这种结合方法,我们分别沿着两种不同的坐标(二面角和RMSD),通过取自同一条TMD轨迹的不同初猜结构进行伞状取样模拟,利用WHAM程序计算得到两条相同的PMF曲线,用于描述丁烷分子从-180°到180°周期转动产生的自由能;同时,将这种方法应用于蛋白体系,我们也得到了一条准确的PMF曲线来描述绒毛蛋白头部域的展开过程的自由能变化,与实验报道一致。这种结合了TMD模拟和伞状取样的计算方法为更多类型的构象转变过程的平均力势计算提供了一种便捷有效的策略。更多还原

【Abstract】 The potential of mean force(PMF) calculations based on the combination of TMD simulations and umbrella samplings as a function of physical coordinates have been applied to explore the detailed pathways and the corresponding free energy profiles for the conformational transition processes of the butane molecule and the 35-residue villin headpiece subdomain(HP35). The accurate PMF profiles for describing the dihedral rotation of butane under both coordinates of dihedral rotation and RMSD variation were obtained based on the different umbrella samplings from the same TMD simulations. The PMF calculation for the unfolding process of the HP35 protein along with the coordinate of the radius of gyration(Rg) was also obtained. The computational method for the PMF calculations combining with TMD simulations and umbrella samplings provided a valuable strategy in investigating detailed conformational transition pathways for other allosteric processes.更多还原