Dynamic void distribution in myoglobin and five mutants.
Globular proteins contain cavities/voids that play specific roles in controlling protein function. Elongated cavities provide migration channels for the transport of ions and small molecules to the active center of a protein or enzyme. Using Monte Carlo and Molecular Dynamics on fully atomistic protein/water models, a new computational methodology is introduced that takes into account the protein's dynamic structure and maps all the cavities in and on the surface. To demonstrate its utility, the methodology is applied to study cavity structure in myoglobin and five of its mutants. Computed cavity and channel size distributions reveal significant differences relative to the wild type myoglobin. Computer visualization of the channels leading to the heme center indicates restricted ligand access for the mutants consistent with the existing interpretations. The new methodology provides a quantitative measure of cavity structure and distributions and can become a valuable tool for the structural characterization of proteins.
Department of Chemical Engineering University of Texas at Austin, Austin, TX 78712, USA.
Yingying
Y
Jiang
Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratories, Los Alamos, New Mexico 87545, United States.
Serdal
S
Kirmizialtin
Department of Chemical Engineering University of Texas at Austin, Austin, TX 78712, USA.
Isaac C
IC
Sanchez
D019295:Computational Biology; D018360:Crystallography, X-Ray; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D009154:Mutation; D009211:Myoglobin / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*; D020836:Protein Structure, Quaternary; D013499:Surface Properties; D013816:Thermodynamics
D009211:Myoglobin