Chowdhury Shibasish, Lee Mathew C, Xiong Guoming, Duan Yong
Department of Chemistry and Biochemistry, Center of Biomedical Research Excellence in Structural and Functional Genomics, University of Delaware, Newark, DE 19716, USA.
J Mol Biol. 2003 Mar 28;327(3):711-7. doi: 10.1016/s0022-2836(03)00177-3.
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 1A 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.
在此，我们报告了对一种最近设计的自主折叠小蛋白tc5b折叠过程进行的100纳秒分子动力学模拟，该模拟采用了基于凝聚相量子力学计算和广义玻恩连续介质溶剂模型开发的新AMBER力场参数集。从其完全伸展的构象开始，我们的模拟产生了一个最终结构，其与核磁共振（NMR）天然结构的主链均方根偏差在1埃以内。值得注意的是，模拟结构在达到该状态后，在模拟的大部分时间里都保持在天然状态。更重要的是，我们的模拟不仅达到了正确的主链构象，而且在侧链堆积构象方面也具有非常高的准确性。这一成果传统上一直是从头算模拟研究面临的挑战。除了对轨迹进行表征外，我们还将结果与实验数据进行了比较。对轨迹的分析表明，这种小蛋白折叠的限速步骤是色氨酸侧链的堆积。
