Maisuradze Gia G, Liwo Adam, Scheraga Harold A
Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA.
J Mol Biol. 2009 Jan 9;385(1):312-29. doi: 10.1016/j.jmb.2008.10.018. Epub 2008 Oct 15.
Protein folding is considered here by studying the dynamics of the folding of the triple beta-strand WW domain from the Formin-binding protein 28. Starting from the unfolded state and ending either in the native or nonnative conformational states, trajectories are generated with the coarse-grained united residue (UNRES) force field. The effectiveness of principal components analysis (PCA), an already established mathematical technique for finding global, correlated motions in atomic simulations of proteins, is evaluated here for coarse-grained trajectories. The problems related to PCA and their solutions are discussed. The folding and nonfolding of proteins are examined with free-energy landscapes. Detailed analyses of many folding and nonfolding trajectories at different temperatures show that PCA is very efficient for characterizing the general folding and nonfolding features of proteins. It is shown that the first principal component captures and describes in detail the dynamics of a system. Anomalous diffusion in the folding/nonfolding dynamics is examined by the mean-square displacement (MSD) and the fractional diffusion and fractional kinetic equations. The collisionless (or ballistic) behavior of a polypeptide undergoing Brownian motion along the first few principal components is accounted for.
本文通过研究来自formin结合蛋白28的三股β链WW结构域的折叠动力学来探讨蛋白质折叠。从非折叠状态开始，以天然或非天然构象状态结束，使用粗粒度联合残基（UNRES）力场生成轨迹。主成分分析（PCA）是一种已确立的用于在蛋白质原子模拟中寻找全局相关运动的数学技术，本文对其在粗粒度轨迹上的有效性进行了评估。讨论了与PCA相关的问题及其解决方案。利用自由能景观研究蛋白质的折叠和非折叠。对不同温度下许多折叠和非折叠轨迹的详细分析表明，PCA对于表征蛋白质的一般折叠和非折叠特征非常有效。结果表明，第一主成分捕获并详细描述了系统的动力学。通过均方位移（MSD）、分数扩散和分数动力学方程研究了折叠/非折叠动力学中的反常扩散。考虑了多肽沿前几个主成分进行布朗运动时的无碰撞（或弹道）行为。
