Mapping the Network of Pathways of CO Diffusion in Myoglobin

摘要

Abstract: The pathways of diffusion of a CO molecule inside a myoglobin protein and toward the solventnare investigated. Specifically, the three-dimensional potential of mean force (PMF or free energy) of thenCO molecule position inside the protein is calculated by using the single-sweep method in concert withnfully resolved atomistic simulations in explicit solvent. The results are interpreted under the assumptionnthat the diffusion of the ligand can be modeled as a navigation on the PMF in which the ligand hops betweennthe PMF local minima following the minimum free energy paths (MFEPs) with rates set by the free energynbarriers that need to be crossed. Here, all the local minima of the PMF, the MFEPs, and the barriers alongnthem are calculated. The positions of the local minima are in good agreement with all the known bindingncavities inside the protein, which indicates that these cavities may indeed serve as dynamical traps insidenthe protein and thereby influence the binding process. In addition, the MFEPs connecting the local PMFnminima show a complicated network of possible pathways of exit of the dissociated CO starting from thenprimary docking site, in which the histidine gate is the closest exit from the binding site for the ligand butnit is not the only possible one.latter is more sensitive than the former.