Ab initio folding simulation of the Trp-cage mini-protein approaches NMR resolution
Ab initio folding simulation of the Trp-cage mini-protein approaches NMR resolution
复制标题
DOI：
10.1016/s0022-2836(03)00177-3
复制
发表时间：
2003-03-28
影响因子：
5.6
通讯作者：
Duan, Y
中科院分区：
文献类型：
--
作者：
Chowdhury, S;Lee, MC;Duan, Y
在这里，我们报告了一个100 ns的分子动力学模拟的折叠过程中，最近设计的一个新的琥珀色力场参数集的基础上开发的凝聚相量子力学计算和广义玻恩连续溶剂模型命名为tc5b的折叠蛋白质。从其完全伸展的构象开始，我们的模拟产生了类似于NMR天然结构的最终结构，主链均方根偏差在1埃以内。值得注意的是，模拟结构在达到状态后的大部分模拟时间内保持在原始状态。更重要的是，我们的模拟不仅达到了正确的主链构象，而且在侧链包装构象的准确度也非常高。这一壮举传统上对从头算模拟研究来说是一个挑战。除了表征的轨迹，我们的结果与实验数据的比较。轨迹的分析表明，该微型蛋白质折叠的限速步骤是色氨酸侧链的包装。(C)2003爱思唯尔科技有限公司。保留所有权利。
Here, we report a 100 ns molecular dynamics simulation of the folding process of a recently designed autonomous-folding mini-protein designated as tc5b with a new AMBER force field parameter set developed based on condensed-phase quantum mechanical calculations and a Generalized Born continuum solvent model. Starting from its fully extended conformation, our simulation has produced a final structure resembling that of NMR native structure to within 1 Angstrom main-chain root mean square deviation. Remarkably, the simulated structure stayed in the native state for most part of the simulation after it reached the state. Of greater significance is that our simulation has not only reached the correct main-chain conformation, but also a very high degree of accuracy in side-chain packing conformation. This feat has traditionally been a challenge for ab initio simulation studies. In addition to characterization of the trajectory, comparison of our results to experimental data is also presented. Analysis of the trajectory suggests that the rate-limiting step of folding of this mini-protein is the packing of the Trp side-chain. (C) 2003 Elsevier Science Ltd. All rights reserved.