Kinetics of Carbon Monoxide Migration and Binding in Solvated Myoglobin as Revealed by Molecular Dynamics Simulations and Quantum Mechanical Calculations

Marco D’Abramo†‡, Alfredo Di Nola§ andAndrea Amadei*
Institut de Recerca Biomdica, Parc Cientific de Barcelona Josep Samitier 1-5, Barcelona 08028 and Barcelona Supercomputing Center Jordi Girona 29, Barcelona 08034, Spain, Departament de Bioquimica, Facultat de Biologia, Universitat de Barcelona, Avgda Diagonal 647 Barcelona 08028, Spain, Dipartimento di Chimica, Universit di Roma “La Sapienza”, P.le A. Moro 5 00185 Rome, Italy, and Departimento di Scienze e Tecnologie Chimiche, Universit di Roma “Tor Vergata”, via della Ricerca Scientifica 00133 Rome, Italy
J. Phys. Chem. B, Article ASAP
DOI: 10.1021/jp903165p
Publication Date (Web): November 24, 2009
Copyright © 2009 American Chemical Society
* To whom correspondence should be addressed. Tel.: 0039 06 72594905. Fax: 0039 06 72594328. E-mail:andrea.amadei@uniroma2.it., † 

Institut de Recerca Biomdica and Barcelona Supercomputing Center Jordi Girona.

FULL TEXT

Abstract

 

By using multiple (independent) molecular dynamics (MD) trajectories (about 500 ns in total) of photolized carbon monoxide (CO) within solvated myoglobin, a quantitative description of CO migration and corresponding kinetics is obtained. MD results combined with previously reported quantum mechanical calculations on the CO−heme binding−unbinding reaction step in myoglobin allowed construction of a detailed quantitative model, shedding light on the kinetic mechanism and relevant steps of CO migration and geminate binding. Finally, the obtained (unbiased) theoretical−computational model is critically compared with the available computational and experimental data for myoglobin in solution.