Multiple conformational states of proteins: a molecular dynamics analysis of myoglobin

Abstract

A molecular dynamics simulation of myoglobin provides the first direct demonstration that the potential energy surface of a protein is characterized by a large number of thermally accessible minima in the neighborhood of the native structure (for example, approximately 2000 minima were sampled in a 300-picosecond trajectory). This is expected to have important consequences for the interpretation of the activity of transport proteins and enzymes. Different minima correspond to changes in the relative orientation of the helices coupled with side-chain rearrangements that preserve the close packing of the protein interior. The conformational space sampled by the simulation is similar to that found in the evolutionary development of the globins. Glasslike behavior is expected at low temperatures. The minima obtained from the trajectory do not satisfy certain criteria for ultrametricity.