Protein dynamics and NMR relaxation: comparison of simulations with experiment

Abstract

Comparisons between molecular dynamics simulations of proteins and experiment have been based on temperature factors^1–5 derived from X-ray spectra and on the stability of hydrogen bonds⁶. Here we present a novel method of testing molecular dynamics simulations against nuclear magnetic resonance (NMR) relaxation measurements, based on the recently developed model-free approach⁷ to the interpretation of NMR data. As NMR relaxation in proteins is determined by dynamics on the picosecond–nanosecond time scale, a comparison of NMR experiments and molecular dynamics simulations that last for less than ∼100ps is more meaningful than previous ones^3–6 involving much longer time scales. We make contact between a molecular dynamics simulation⁸ and a ¹³C-NMR relaxation study⁹ of pancreatic trypsin inhibitor (PTI) by comparing generalized order parameters (which are measures of the extent of angular motion of the bonds) extracted from the relaxation data⁹ with those calculated¹⁰ from a 96-ps trajectory⁸. We show that the theoretical order parameters indicate less motion than their experimental counterparts. The relative flexibility of the residues studied, however, is reasonably well described by the simulation.