In-silico assessment of protein-protein electron transfer. a case study: cytochrome c peroxidase--cytochrome c

PLoS Comput Biol. 2013;9(3):e1002990. doi: 10.1371/journal.pcbi.1002990. Epub 2013 Mar 21.

Abstract

The fast development of software and hardware is notably helping in closing the gap between macroscopic and microscopic data. Using a novel theoretical strategy combining molecular dynamics simulations, conformational clustering, ab-initio quantum mechanics and electronic coupling calculations, we show how computational methodologies are mature enough to provide accurate atomistic details into the mechanism of electron transfer (ET) processes in complex protein systems, known to be a significant challenge. We performed a quantitative study of the ET between Cytochrome c Peroxidase and its redox partner Cytochrome c. Our results confirm the ET mechanism as hole transfer (HT) through residues Ala194, Ala193, Gly192 and Trp191 of CcP. Furthermore, our findings indicate the fine evolution of the enzyme to approach an elevated turnover rate of 5.47 × 10(6) s(-1) for the ET between Cytc and CcP through establishment of a localized bridge state in Trp191.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computer Simulation
  • Cytochrome-c Peroxidase / chemistry*
  • Cytochrome-c Peroxidase / metabolism*
  • Cytochromes c / chemistry*
  • Cytochromes c / metabolism*
  • Electron Transport
  • Horses
  • Molecular Dynamics Simulation
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Oxidation-Reduction
  • Protein Conformation

Substances

  • Multiprotein Complexes
  • Cytochromes c
  • Cytochrome-c Peroxidase

Grants and funding

Computational resources were provided by the Barcelona Supercomputing Center. Work was supported by startup funds from the Barcelona Supercomputer Center, by the Spanish Ministry of Education and Science to VG through the project CTQ2010-18123 as well as to AAV through the project CTQ2009-12346. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.