Sidechain rotational isomerization in proteins. Dynamic simulation with solvent surroundings.

Molecular dynamics simulations are used to study the rotational isomerization of the tyrosine 35 ring in bovine pancreatic trypsin inhibitor immersed in liquid water. Inclusion of the solvent surroundings improves the agreement with experimental results significantly, although the theoretical free energy barrier (13 kcal/mol at 300K) is still approximately 3 kcal/mol below that found by nuclear magnetic resonance studies. This remaining discrepancy will probably be eliminated in future calculations by the use of a more accurate model for the hydrogen atoms on the tyrosine ring. An important finding in the present work is that frictional effects due to solvent damping appear to be small for the tyrosine 35 ring, which is largely but not completely buried in the protein surface.