Andrec Michael, Felts Anthony K, Gallicchio Emilio, Levy Ronald M
Department of Chemistry and Chemical Biology and BIOMAPS Institute for Quantitative Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Proc Natl Acad Sci U S A. 2005 May 10;102(19):6801-6. doi: 10.1073/pnas.0408970102. Epub 2005 Mar 30.
We present an approach to the study of protein folding that uses the combined power of replica exchange simulations and a network model for the kinetics. We carry out replica exchange simulations to generate a large ( approximately 10(6)) set of states with an all-atom effective potential function and construct a kinetic model for folding, using an ansatz that allows kinetic transitions between states based on structural similarity. We use this network to perform random walks in the state space and examine the overall network structure. Results are presented for the C-terminal peptide from the B1 domain of protein G. The kinetics is two-state after small temperature perturbations. However, the coil-to-hairpin folding is dominated by pathways that visit metastable helical conformations. We propose possible mechanisms for the alpha-helix/beta-hairpin interconversion.
我们提出了一种研究蛋白质折叠的方法，该方法利用了副本交换模拟和动力学网络模型的联合力量。我们进行副本交换模拟，以使用全原子有效势函数生成大量（约10^6）的状态集，并使用一种假设构建折叠的动力学模型，该假设允许基于结构相似性在状态之间进行动力学转变。我们使用这个网络在状态空间中进行随机游走，并检查整体网络结构。给出了来自蛋白质G的B1结构域的C末端肽的结果。在小的温度扰动后，动力学是两态的。然而，从无规卷曲到发夹的折叠主要由访问亚稳螺旋构象的途径主导。我们提出了α-螺旋/β-发夹相互转换的可能机制。
