Suenaga Atsushi, Narumi Tetsu, Futatsugi Noriyuki, Yanai Ryoko, Ohno Yousuke, Okimoto Noriaki, Taiji Makoto
High-Performance Molecular Simulation Team, Computational and Experimental System Biology Group, RIKEN Genomic Sciences Center, 61-1 Ono-cho, Tsurumi, Yokohama, Kanagawa 230-0046, Japan.
Chem Asian J. 2007 May 4;2(5):591-8. doi: 10.1002/asia.200600385.
Short peptides that fold into beta-hairpins are ideal model systems for investigating the mechanism of protein folding because their folding process shows dynamics typical of proteins. We performed folding, unfolding, and refolding molecular dynamics simulations (total of 2.7 micros) of the 10-residue beta-hairpin peptide chignolin, which is the smallest beta-hairpin structure known to be stable in solution. Our results revealed the folding mechanism of chignolin, which comprises three steps. First, the folding begins with hydrophobic assembly. It brings the main chain together; subsequently, a nascent turn structure is formed. The second step is the conversion of the nascent turn into a tight turn structure along with interconversion of the hydrophobic packing and interstrand hydrogen bonds. Finally, the formation of the hydrogen-bond network and the complete hydrophobic core as well as the arrangement of side-chain-side-chain interactions occur at approximately the same time. This three-step mechanism appropriately interprets the folding process as involving a combination of previous inconsistent explanations of the folding mechanism of the beta-hairpin, that the first event of the folding is formation of hydrogen bonds and the second is that of the hydrophobic core, or vice versa.
折叠成β-发夹结构的短肽是研究蛋白质折叠机制的理想模型系统，因为它们的折叠过程展现出蛋白质典型的动力学特征。我们对由10个残基组成的β-发夹肽chignolin进行了折叠、解折叠和重折叠分子动力学模拟（总计2.7微秒），chignolin是已知在溶液中稳定的最小β-发夹结构。我们的结果揭示了chignolin的折叠机制，该机制包括三个步骤。首先，折叠始于疏水组装。它使主链聚集在一起；随后，形成一个新生的转角结构。第二步是新生转角转变为紧密转角结构，同时疏水堆积和链间氢键发生相互转换。最后，氢键网络、完整的疏水核心的形成以及侧链-侧链相互作用的排列几乎同时发生。这种三步机制恰当地解释了折叠过程，该过程涉及先前对β-发夹折叠机制的不一致解释的结合，即折叠的第一个事件是氢键的形成，第二个事件是疏水核心的形成，或者反之亦然。
