What Contributions to Protein Side-chain Dynamics are Probed by NMR Experiments? A Molecular Dynamics Simulation Analysis

Mol. 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 expts.  The results reproduce the variation in core side-chain dynamics obsd. by NMR and highlight the relevance of anharmonic motion and transitions between local min. for explaining NMR side-chain order parameters.  A method is described for calcg. converged order parameters by use of replica exchange mol. 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 vol., 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 anal. of published order parameters supports the conclusions drawn from the simulations.