多种蛋白质的全原子从头折叠

All-atom ab initio folding of a diverse set of proteins.

作者信息

Yang Jae Shick, Chen William W, Skolnick Jeffrey, Shakhnovich Eugene I

机构信息

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.

出版信息

Structure. 2007 Jan;15(1):53-63. doi: 10.1016/j.str.2006.11.010.

DOI:10.1016/j.str.2006.11.010

PMID:17223532

Abstract

Natural proteins fold to a unique, thermodynamically dominant state. Modeling of the folding process and prediction of the native fold of proteins are two major unsolved problems in biophysics. Here, we show successful all-atom ab initio folding of a representative diverse set of proteins by using a minimalist transferable-energy model that consists of two-body atom-atom interactions, hydrogen bonding, and a local sequence-energy term that models sequence-specific chain stiffness. Starting from a random coil, the native-like structure was observed during replica exchange Monte Carlo (REMC) simulation for most proteins regardless of their structural classes; the lowest energy structure was close to native-in the range of 2-6 A root-mean-square deviation (rmsd). Our results demonstrate that the successful folding of a protein chain to its native state is governed by only a few crucial energetic terms.

摘要

天然蛋白质折叠成一种独特的、热力学上占主导地位的状态。蛋白质折叠过程的建模和天然折叠结构的预测是生物物理学中两个主要的未解决问题。在此，我们通过使用一种极简的可转移能量模型，展示了一组具有代表性的不同蛋白质的全原子从头折叠成功，该模型由双体原子 - 原子相互作用、氢键以及一个模拟序列特异性链刚度的局部序列 - 能量项组成。从无规卷曲开始，在复制交换蒙特卡罗（REMC）模拟过程中，大多数蛋白质无论其结构类别如何，都观察到了类似天然的结构；最低能量结构与天然结构接近——均方根偏差（rmsd）在2 - 6埃范围内。我们的结果表明，蛋白质链成功折叠成其天然状态仅由少数几个关键的能量项决定。