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Updated: May 8, 2026

NMR 15N Relaxation Experiments for the Investigation of Picosecond to Nanoseconds Structural Dynamics of Proteins
Published on: November 1, 2024
Microscopic insights into the NMR relaxation-based protein conformational entropy meter
Vignesh Kasinath1, Kim A Sharp, A Joshua Wand
1Graduate Group in Biochemistry and Molecular Biophysics and the Johnson Research Foundation and Department of Biochemistry & Biophysics, University of Pennsylvania Perelman School of Medicine , Philadelphia 19104, United States.
Abstract:
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--the NMR-derived generalized order parameters--as a proxy from which to derive changes in protein conformational entropy.
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