Park Hwangseo, Lee Sangyoub
School of Chemistry and Molecular Engineering, Seoul National University, Korea.
Biophys Chem. 2005 Apr 22;114(2-3):191-7. doi: 10.1016/j.bpc.2004.12.006. Epub 2004 Dec 22.
Comparative protein structure modeling and free energy perturbation simulation have been applied in a consecutive manner to investigate the mutation-induced stabilization of membrane proteins (MPs) in aqueous solution without knowledge of their three-dimensional structures. The calculated difference in protein solvation free energy between the wild type and a mutant compares well with their relative thermodynamic stabilities in solution. For monomeric MPs, a mutant reveals a higher stability than the wild type if the calculated solvation free energy indicates a favorable change. On the contrary, for oligomeric MPs the stability of a mutant increases as the solvation free energy of a mutated monomer becomes less favorable, indicating that the oligomeric MP mutant would be stabilized in solution due to the reduced desolvation cost for oligomerization. The present computational strategy is expected to find its way as a useful tool for assessing the relative stability of a mutant MP with respect to its wild type in solution.
比较蛋白质结构建模和自由能扰动模拟已被连续应用于研究水溶液中膜蛋白（MPs）的突变诱导稳定性，而无需了解其三维结构。计算得到的野生型和突变体之间蛋白质溶剂化自由能的差异与它们在溶液中的相对热力学稳定性比较吻合。对于单体MPs，如果计算得到的溶剂化自由能表明有有利变化，则突变体显示出比野生型更高的稳定性。相反，对于寡聚MPs，随着突变单体的溶剂化自由能变得更不利，突变体的稳定性增加，这表明寡聚MP突变体由于寡聚化的去溶剂化成本降低而在溶液中得到稳定。预计目前的计算策略将成为评估溶液中突变MP相对于其野生型的相对稳定性的有用工具。
