Zhang Jian, Qin Meng, Wang Wei
National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University, China.
Proteins. 2006 Mar 15;62(3):672-85. doi: 10.1002/prot.20813.
The folding process of trpzip2 beta-hairpin is studied by the replica exchange molecular dynamics (REMD) and normal MD simulations, aiming to understand the folding mechanism of this unique small, stable, and fast folder, as well as to reveal the general principles in the folding of beta-hairpins. According to our simulations, the TS ensemble is mainly characterized by a largely formed turn and the interaction between the inner pair of hydrophobic core residues. The folding is a zipping up of hydrogen bonds. However, the nascent turn has to be stabilized by the partially formed hydrophobic core to cross the TS. Thus our folding picture is in essence a blend of hydrogen bond-centric and hydrophobic core-centric mechanism. Our simulations provide a direct evidence for a very recent experiment (Du et al., Proc Natl Acad Sci USA 2004;101:15915-15920), which suggests that the turn formation is the rate-limiting step for beta-hairpin folding and the unfolding is mainly determined by the hydrophobic interactions. Besides, the relationship between hydrogen bond stabilities and their relative importance in folding are investigated. It is found that the hydrogen bonds with higher stabilities need not play more important roles in the folding process, and vice versa.
通过副本交换分子动力学（REMD）和常规分子动力学模拟研究了trpzip2β-发夹的折叠过程，旨在了解这种独特的小尺寸、稳定且折叠快速的分子的折叠机制，同时揭示β-发夹折叠的一般原理。根据我们的模拟，过渡态系综的主要特征是形成了一个大致的转角以及内部一对疏水核心残基之间的相互作用。折叠过程是氢键的逐步形成。然而，新生的转角必须通过部分形成的疏水核心来稳定，以便跨越过渡态。因此，我们的折叠图景本质上是一种以氢键为中心和以疏水核心为中心机制的融合。我们的模拟为最近的一项实验（Du等人，《美国国家科学院院刊》2004年；101:15915 - 15920）提供了直接证据，该实验表明转角的形成是β-发夹折叠的限速步骤，而展开主要由疏水相互作用决定。此外，还研究了氢键稳定性与其在折叠过程中相对重要性之间的关系。结果发现，稳定性较高的氢键在折叠过程中不一定起更重要的作用，反之亦然。
