Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
J Chem Phys. 2012 Apr 7;136(13):135102. doi: 10.1063/1.3698164.
Solvent effect on protein conformation and folding mechanism of E6-associated protein (E6ap) peptide are investigated using a recently developed charge update scheme termed as adaptive hydrogen bond-specific charge (AHBC). On the basis of the close agreement between the calculated helix contents from AHBC simulations and experimental results, we observed based on the presented simulations that the two ends of the peptide may simultaneously take part in the formation of the helical structure at the early stage of folding and finally merge to form a helix with lowest backbone RMSD of about 0.9 Å in 40% 2,2,2-trifluoroethanol solution. However, in pure water, the folding may start at the center of the peptide sequence instead of at the two opposite ends. The analysis of the free energy landscape indicates that the solvent may determine the folding clusters of E6ap, which subsequently leads to the different final folded structure. The current study demonstrates new insight to the role of solvent in the determination of protein structure and folding dynamics.
使用最近开发的电荷更新方案——自适应氢键特定电荷 (AHBC)，研究了溶剂对 E6 相关蛋白 (E6ap) 肽的蛋白质构象和折叠机制的影响。基于 AHBC 模拟计算的螺旋含量与实验结果之间的高度一致性，我们根据所呈现的模拟结果观察到，在折叠的早期阶段，肽的两端可能同时参与螺旋结构的形成，最终合并形成一条螺旋，其主链 RMSD 最低约为 0.9 Å，在 40%的 2,2,2-三氟乙醇溶液中。然而，在纯水中，折叠可能从肽序列的中心开始，而不是从两个相对的末端开始。自由能景观的分析表明，溶剂可能决定 E6ap 的折叠簇，进而导致不同的最终折叠结构。本研究为溶剂在蛋白质结构和折叠动力学中的作用提供了新的见解。
