Jordi Cohen, Anton Arkhipov, Rosemary Braun, and Klaus Schulten.
Imaging the migration pathways for O2, CO, NO, and Xe
inside myoglobin.
Biophysical Journal, 91:1844-1857, 2006.
(PMC: 1544290)
COHE2006
Myoglobin (Mb) is perhaps the most studied protein, experimentally and theoretically. Despite the wealth of known details regarding the gas migration processes inside Mb, there exists no fully conclusive picture of these pathways. We address this deficiency by presenting a complete map of all the gas migration pathways inside Mb for small gas ligands (O2, NO, CO, and Xe). To accomplish this, we introduce a computational approach for studying gas migration, which we call implicit ligand sampling. Rather than simulating actual gas migration events, we infer the location of gas migration pathways based on a free-energy perturbation approach applied to simulations of Mb's dynamical fluctuations at equilibrium in the absence of ligand. The method provides complete three-dimensional maps of the potential of mean force of gas ligand placement anywhere inside a protein-solvent system. From such free-energy maps we identify each gas docking site, the pathways between these sites, to the heme and to the external solution. Our maps match previously known features of these pathways in Mb, but also point to the existence of additional exits from the protein matrix in regions that are not easily probed by experiment. We also compare the pathway maps of Mb for different gas ligands and for different animal species.
Download Full Text
The manuscripts available on our site are provided for your personal
use only and may not be retransmitted or redistributed without written
permissions from the paper's publisher and author. You may not upload any
of this site's material to any public server, on-line service, network, or
bulletin board without prior written permission from the publisher and
author. You may not make copies for any commercial purpose. Reproduction
or storage of materials retrieved from this web site is subject to the
U.S. Copyright Act of 1976, Title 17 U.S.C.
