Thursday, January 2, 2014

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

Vignesh Kasinath, Kim A. Sharp, and A. Joshua Wand Journal of the American Chemical Society 2013, 135, 15092
Contributed by +Jan Jensen

Order parameters measured by NMR report on the local fluctuations of protein structures and should therefore be related to entropy. This study uses molecular dynamics (MD) simulations to obtain a quantitative relationship between conformational side chain entropy ($S_{sc}$) and Lipari-Szabo methyl group squared generalized order parameters ($O^2$).

First the authors demonstrate that MD simulations can reproduce experimentally measured $O^2$ values for 7 different proteins, with an $R^2$ of 0.92.

Second the authors demonstrate a linear correlation between the total $S_{sc}$ and computed $O^2$ values, both for methyl containing side chains ($R^2$ = 0.90) and for all side chains ($R^2$ = 0.91).

Based on these finding the authors re-analyzed data from two previously published studies, and extracted a similarly quantitative linear correlation ($R^2$ = 0.95) between the molecular entropy change ($\Delta S_{tot}-\Delta S_{solv}$) and the measured change in $O^2$ values for protein-protein and protein-DNA binding.  This suggest that both entropy changes are dominated by the changes in conformational side-chain entropy.

The method looks like a very powerful tool for obtaining detailed quantitative structural understanding of entropy changes in biomolecular processes.