Luo Zhonglin, Ding Jiandong, Zhou Yaoqi
Key Laboratory of Molecular Engineering of Polymers, Ministry of Education, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai, China.
Biophys J. 2007 Sep 15;93(6):2152-61. doi: 10.1529/biophysj.106.102095. Epub 2007 May 18.
We study the folding thermodynamics and kinetics of the Pin1 WW domain, a three-stranded beta-sheet protein, by using all-atom (except nonpolar hydrogens) discontinuous molecular dynamics simulations at various temperatures with a Gō model. The protein exhibits a two-state folding kinetics near the folding transition temperature. A good agreement between our simulations and the experimental measurements by the Gruebele group has been found, and the simulation sheds new insights into the structure of transition state, which is hard to be straightforwardly captured in experiments. The simulation also reveals that the folding pathways at approximately the transition temperature and at low temperatures are much different, and an intermediate state at a low temperature is predicted. The transition state of this small beta-protein at its folding transition temperature has a well-established hairpin 1 made of beta1 and beta2 strands while its low-temperature kinetic intermediate has a formed hairpin 2 composed of beta2 and beta3 strands. Theoretical results are compared with other simulation results as well as available experimental data. This study confirms that specific side-chain packing in an all-atom Gō model can yield a reasonable prediction of specific folding kinetics for a given protein. Different folding behaviors at different temperatures are interpreted in terms of the interplay of entropy and enthalpy in folding process.
我们使用全原子（除了非极性氢）间断分子动力学模拟，采用Gō模型在不同温度下研究了Pin1 WW结构域（一种三链β-折叠蛋白）的折叠热力学和动力学。该蛋白在折叠转变温度附近呈现两态折叠动力学。我们的模拟结果与格鲁贝勒团队的实验测量结果吻合良好，并且该模拟为过渡态结构提供了新的见解，而过渡态结构在实验中很难直接捕捉到。模拟还揭示了大约在转变温度和低温下的折叠途径有很大不同，并预测了低温下存在一个中间态。这种小β-蛋白在其折叠转变温度下的过渡态具有由β1和β2链形成的成熟发夹1，而其低温动力学中间态具有由β2和β3链组成的已形成发夹2。将理论结果与其他模拟结果以及现有的实验数据进行了比较。这项研究证实，在全原子Gō模型中特定的侧链堆积能够对给定蛋白的特定折叠动力学做出合理预测。不同温度下的不同折叠行为根据折叠过程中熵和焓的相互作用来解释。
