蛋白质突变体的稳定性能否通过自由能计算来预测？

Can the stability of protein mutants be predicted by free energy calculations?

作者信息

Shi Y Y, Mark A E, Wang C X, Huang F, Berendsen H J, van Gunsteren W F

机构信息

Department of Biology, University of Science and Technology of China, Anhui.

出版信息

Protein Eng. 1993 Apr;6(3):289-95. doi: 10.1093/protein/6.3.289.

DOI:10.1093/protein/6.3.289

PMID:8506263

Abstract

The use of free energy simulation techniques in the study of protein stability is critically evaluated. Results from two simulations of the thermostability mutation Asn218 to Ser218 in Subtilisin are presented. It is shown that components of the free energy change can be highly sensitive to the computational details of the simulation leading to the conclusion that free energy calculations cannot currently be used to reliably predict protein stability. The different factors that undermine the reliability are discussed.

摘要

对自由能模拟技术在蛋白质稳定性研究中的应用进行了严格评估。展示了枯草杆菌蛋白酶中热稳定性突变Asn218至Ser218的两次模拟结果。结果表明，自由能变化的组成部分可能对模拟的计算细节高度敏感，从而得出目前自由能计算无法可靠预测蛋白质稳定性的结论。讨论了破坏可靠性的不同因素。