Quantifying the importance of protein conformation on ligand migration in myoglobin.

ABSTRACT: Myoglobin (Mb) is a model system for ligand binding and migration. The energy barriers (?G) for ligand migration in Mb have been studied in the past by experiment and theory and significant differences between different approaches were found. From experiment, it is known that Mb can assume a large number of conformational substates. In this work, these substates are investigated as a possible source of the differences in migration barriers. We show that the initial structure significantly affects the calculated ?G for a particular transition and that fluctuations in barrier heights ??G are of similar magnitude as the free energy barriers themselves. The sensitivity of ?G to the initial structure is compared to other sources of errors. Different protein structures can affect the calculated ?G by up to 4 kcal/mol, whereas differences between simple point charge models and more elaborate multipolar charge models for the CO-ligand are smaller by a factor of two. Analysis of the structural changes underlying the large effect of the conformational substate reveals the importance of coupling between protein and ligand motion for migration.

SUBMITTER: Plattner N 

PROVIDER: S-EPMC3260668 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature