Microscopic Insights into the NMR Relaxation-Based Protein Conformational Entropy Meter

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• 作者：Vignesh Kasinath ; Kim A. Sharp ; A. Joshua Wand
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：October 9, 2013
• 年：2013
• 卷：135
• 期：40
• 页码：15092-15100
• 全文大小：358K
• 年卷期：v.135,no.40(October 9, 2013)
• ISSN：1520-5126

文摘

Conformational entropy is a potentially important thermodynamic parameter contributing to protein function. Quantitative measures of conformational entropy are necessary for an understanding of its role but have been difficult to obtain. An empirical method that utilizes changes in conformational dynamics as a proxy for changes in conformational entropy has recently been introduced. Here we probe the microscopic origins of the link between conformational dynamics and conformational entropy using molecular dynamics simulations. Simulation of seven proteins gave an excellent correlation with measures of side-chain motion derived from NMR relaxation. The simulations show that the motion of methyl-bearing side chains are sufficiently coupled to that of other side chains to serve as excellent reporters of the overall side-chain conformational entropy. These results tend to validate the use of experimentally accessible measures of methyl motion鈥攖he NMR-derived generalized order parameters鈥攁s a proxy from which to derive changes in protein conformational entropy.