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Updated: Aug 18, 2026

NMR 15N Relaxation Experiments for the Investigation of Picosecond to Nanoseconds Structural Dynamics of Proteins
Published on: November 1, 2024
What contributions to protein side-chain dynamics are probed by NMR experiments? A molecular dynamics simulation
Robert B Best1, Jane Clarke, Martin Karplus
1MRC Centre for Protein Engineering, Department of Chemistry, Lensfield Road, Cambridge, CB2 1EW, UK.
Abstract:
Molecular dynamics simulations of the structurally homologous proteins TNfn3 and FNfn10 have been used to investigate the contributions to side-chain dynamics measured by NMR relaxation experiments. The results reproduce the variation in core side-chain dynamics observed by NMR and highlight the relevance of anharmonic motion and transitions between local minima for explaining NMR side-chain order parameters. A method is described for calculating converged order parameters by use of replica exchange molecular dynamics in conjunction with an implicit solvent model. These simulations allow the influence of various factors, such as the flexibility of side-chains and their free volume, on the mobility to be tested by perturbing the system. Deletion mutations are found to have the largest effect on the more densely packed FNfn10. Some counterintuitive effects are seen, such as an increase in order parameters close to deletion mutation sites, but these can be rationalized in terms of direct interactions with the modified side-chains. A statistical analysis of published order parameters supports the conclusions drawn from the simulations.
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