Correlation between changes in nuclear magnetic resonance order parametersand conformational entropy: Molecular dynamics simulations of native and denatured staphylococcal nuclease

Recent work has suggested that changes in NMR order parameters may quantita tively reflect changes in the conformational entropy of a protein ensemble. The extent of the mathematical relationship between local entropy changes as seen by NMR order parameters and the full protein entropy change is a co mplex issue. As a step towards a fuller understanding of this problem, mole cular dynamics calculations of both native and denatured staphylococcal nuc lease were performed. The N-H bond vector motion, in both explicit and impl icit solvent, was analyzed to estimate local and global entropy changes. Th e calculated N-H bond vector order parameters from simulation agreed on ave rage with experimental values for both native and denatured structures. How ever, the inverted-U profile of order parameters versus residue number obse rved experimentally for denatured nuclease was only partially reproduced by simulation of compact denatured structures. Comparisons made across the fu ll set of simulations revealed a correlation between the N-H order paramete r-based conformational entropy change and the total quasiharmonic-based con formational entropy change between the native and denatured structures. The calculations showed that about 25% of the total entropy change was reflect ed by changes in simulated S-2 values. This result suggests that NMR-derive d order parameters may be used to provide a reasonable estimate of the tota l conformational entropy change on protein folding. Proteins 2000;38:123-13 3. (C) 2000 Wiley-Liss, Inc.