Bioinformatics Team, Scientific and Engineering Computing Group, Centre for Development of Advanced Computing, Pune University Campus, Ganeshkhind, Pune - 411007, Maharashtra, India.
J Biomol Struct Dyn. 2011 Jun;28(6):845-60. doi: 10.1080/07391102.2011.10508612.
Reaching the experimental time scale of millisecond is a grand challenge for protein folding simulations. The development of advanced Molecular Dynamics techniques like Replica Exchange Molecular Dynamics (REMD) makes it possible to reach these experimental timescales. In this study, an attempt has been made to reach the multi microsecond simulation time scale by carrying out folding simulations on a three helix bundle protein, Villin, by combining REMD and Amber United Atom model. Twenty replicas having different temperatures ranging from 295 K to 390 K were simulated for 1.5 µs each. The lowest Root Mean Square Deviation (RMSD) structure of 2.5 Å was obtained with respect to native structure (PDB code 1VII), with all the helices formed. The folding population landscapes were built using segment-wise RMSD and Principal Components as reaction coordinates. These analyses suggest the two-stage folding for Villin. The combination of REMD and Amber United Atom model may be useful to understand the folding mechanism of various fast folding proteins.
达到毫秒级的实验时间尺度是蛋白质折叠模拟的一大挑战。Replica Exchange Molecular Dynamics（REMD）等先进分子动力学技术的发展使得达到这些实验时间尺度成为可能。在这项研究中，通过结合 REMD 和 Amber 统一原子模型，对三叶螺旋束蛋白 Villin 进行折叠模拟，尝试达到多微秒的模拟时间尺度。模拟了 20 个温度从 295 K 到 390 K 不等的副本，每个副本的模拟时间为 1.5 µs。与天然结构（PDB 代码 1VII）相比，获得了最低的 RMSD 结构为 2.5 Å，所有螺旋都形成了。使用分段 RMSD 和主成分作为反应坐标构建了折叠种群景观。这些分析表明 Villin 的折叠存在两阶段。REMD 和 Amber 统一原子模型的结合可能有助于理解各种快速折叠蛋白质的折叠机制。
