Exploring the energy landscape of protein folding using replica-exchange and conventional molecular dynamics simulations
Exploring the energy landscape of protein folding using replica-exchange and conventional molecular dynamics simulations
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DOI：
10.1016/j.jsb.2006.10.002
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发表时间：
2007-03-01
影响因子：
3
通讯作者：
Daggett, Valerie
中科院分区：
文献类型：
--
作者：
Beck, David A. C.;White, George W. N.;Daggett, Valerie
两个独立的复制交换分子动力学（REMD）模拟与明确的水模型进行的色氨酸笼迷你蛋白。在第一个REMD模拟中，复制品从天然构象开始，而在第二个中，它们从规范构象开始。最初，第一次模拟产生的结果与之前发表的两次REMD模拟的结果在定性上相似：蛋白质似乎过度稳定，预测的熔化温度比实验值315 K高50-150 K。然而，随着第一次REMD模拟的进展，蛋白质在所有温度下都展开。在我们的第二个REMD模拟中，从规范构象开始，没有明显折叠的证据。从展开到折叠状态的转变没有发生在这些模拟的时间尺度上，尽管预期的改进，在传统的分子动力学（MD）模拟的采样REMD。组合的1.42 μ s的模拟时间不足以使具有不同起始结构的REMD模拟收敛。还进行了在一定温度范围内的常规MID模拟。与REMD相比，传统的MD模拟提供了与实验吻合良好的Tm的估计。此外，传统的MD是一小部分的成本REMD和连续的，现实的路径展开过程中原子分辨率获得。(c)2006年爱思唯尔公司All rights reserved.
Two independent replica-exchange molecular dynamics (REMD) simulations with an explicit water model were performed of the Trp-cage mini-protein. In the first REMD simulation, the replicas started from the native conformation, while in the second they started from a normative conformation. Initially, the first simulation yielded results qualitatively similar to those of two previously published REMD simulations: the protein appeared to be over-stabilized, with the predicted melting temperature 50-150 K higher than the experimental value of 315 K. However, as the first REMD simulation progressed, the protein unfolded at all temperatures. In our second REMD simulation, which starts from a normative conformation, there was no evidence of significant folding. Transitions from the unfolded to the folded state did not occur on the timescale of these simulations, despite the expected improvement in sampling of REMD over conventional molecular dynamics (MD) simulations. The combined 1.42 mu s of simulation time was insufficient for REMD simulations with different starting structures to converge. Conventional MID simulations at a range of temperatures were also performed. In contrast to REMD, the conventional MD simulations provide an estimate of Tm in good agreement with experiment. Furthermore, the conventional MD is a fraction of the cost of REMD and continuous, realistic pathways of the unfolding process at atomic resolution are obtained. (c) 2006 Elsevier Inc. All rights reserved.