Protein folding pathways from replica exchange simulations and a kinetic network model
Protein folding pathways from replica exchange simulations and a kinetic network model
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DOI：
10.1073/pnas.0408970102
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发表时间：
2005-05-10
影响因子：
11.1
通讯作者：
Levy, RM
中科院分区：
文献类型：
--
作者：
Andrec, M;Felts, AK;Levy, RM
我们提出了一种研究蛋白质折叠的方法，该方法使用了复制品交换模拟的组合功率和动力学的网络模型。我们进行复制交换模拟，以生成具有全原子有效势能的大型（至10（6）个状态，并使用ANSATZ构建一个动力学模型，并使用ANSATZ允许基于结构相似性的状态之间的动力学转变。我们使用此网络在状态空间中进行随机步行并检查整个网络结构。从蛋白质G的B1结构域中为C末端肽提出了结果。在较小的温度扰动之后，动力学是两态。但是，线圈到发的折叠主要由访问亚稳态构象的途径主导。我们提出了Alpha-Helix/ beta-hairpin互续的可能机制。
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 (approximate to 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.