A1 Refereed original research article in a scientific journal
Parameterization of the prosthetic redox centers of the bacterial cytochrome bc(1) complex for atomistic molecular dynamics simulations
Authors: Kaszuba K, Postila PA, Cramariuc O, Sarewicz M, Osyczka A, Vattulainen I, Rog T
Publisher: SPRINGER
Publication year: 2013
Journal: Theoretical Chemistry Accounts: Theory, Computation, and Modeling
Journal name in source: THEORETICAL CHEMISTRY ACCOUNTS
Journal acronym: THEOR CHEM ACC
Article number: ARTN 1370
Volume: 132
Number of pages: 13
ISSN: 1432-881X
DOI: https://doi.org/10.1007/s00214-013-1370-8
Abstract
Cytochrome (cyt) bc(1) is a multi-subunit membrane protein complex that is a vital component of the respiratory and photosynthetic electron transfer chains both in bacteria and eukaryotes. Although the complex's dimer structure has been solved using X-ray crystallography, it has not yet been studied in large-scale classical molecular dynamics (MD) simulations. In part, this is due to lack of suitable force field parameters, centered atomic point charges in particular, for the complex's prosthetic redox centers. Accurate redox center charges are needed to depict realistically the inter-molecular interactions at different redox stages of the cyt bc(1) complex. Accordingly, here we present high-precision atomic point charges for the metal centers of the cyt bc(1) complex of Rhodobacter capsulatus derived from extensive density functional theory calculations, fitted using the restrained electrostatic potential methodology and combined with the CHARMM force field parameters. We also provide the Hartree-Fock charges for all substrate forms (quinol, quinone, and semiquinone) and the inhibitors antimycin and stigmatellin of the bacterial bc(1) complex. The accuracy of the parameterization scheme was verified by running a 200-ns MD simulation encompassing the entire cyt bc(1) complex embedded in a lipid bilayer and solvated with explicit water. The results indicate that these meticulously derived parameters are ready for running extensive MD simulations encompassing all biologically relevant stages of the cyt bc(1) complex reaction cycle.
Cytochrome (cyt) bc(1) is a multi-subunit membrane protein complex that is a vital component of the respiratory and photosynthetic electron transfer chains both in bacteria and eukaryotes. Although the complex's dimer structure has been solved using X-ray crystallography, it has not yet been studied in large-scale classical molecular dynamics (MD) simulations. In part, this is due to lack of suitable force field parameters, centered atomic point charges in particular, for the complex's prosthetic redox centers. Accurate redox center charges are needed to depict realistically the inter-molecular interactions at different redox stages of the cyt bc(1) complex. Accordingly, here we present high-precision atomic point charges for the metal centers of the cyt bc(1) complex of Rhodobacter capsulatus derived from extensive density functional theory calculations, fitted using the restrained electrostatic potential methodology and combined with the CHARMM force field parameters. We also provide the Hartree-Fock charges for all substrate forms (quinol, quinone, and semiquinone) and the inhibitors antimycin and stigmatellin of the bacterial bc(1) complex. The accuracy of the parameterization scheme was verified by running a 200-ns MD simulation encompassing the entire cyt bc(1) complex embedded in a lipid bilayer and solvated with explicit water. The results indicate that these meticulously derived parameters are ready for running extensive MD simulations encompassing all biologically relevant stages of the cyt bc(1) complex reaction cycle.
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