CHANNELS, RECEPTORS, AND ELECTRICAL SIGNALING |
REORGANIZATION AND CONFORMATIONAL CHANGES IN THE REDUCTION OF TETRAHEME CYTOCHROMES
A. Sofia F Oliveira 1, Vitor H Teixeira 1, António M Baptista 1 and Claudio M. Soares 1*
1 Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa
* To whom correspondence should be addressed. E-mail: claudio{at}itqb.unl.pt.
Submitted on April 22, 2005
Revised on June 28, 2005
Accepted on 6 September 2005
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Abstract |
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Molecular dynamics simulation (MD) constitutes an alternative to time-consuming experiments for studying conformational changes. We apply MD on a redox system where experimental information exists for the fully oxidized and fully reduced states: tetraheme cytochrome c3. Instead of doing one simulation for each state, we apply ten 4ns replicas for both states, which provides robust statistics to characterize the redox changes. Besides these long simulations, we perform 120 short ones (50ps), where an equilibrated oxidized state is perturbed to a reduced state. This allows the application of a non-equilibrium method, the subtraction technique, which makes possible to characterize the different timescales of conformational changes. Reduction induces conformational changes in the N-terminus and on the loops spanning from residues 36-42 and 88-93, which correlate very well with experiments, demonstrating the applicability of this methodology. We also analyze the effect of reduction on hydrogen bonds, solvent accessible surface and bound water, the changes being found to involve the hemes and propionate groups. Redox-induced protonation is also investigated, by protonating the propionates D from hemes I and IV. While this change in the former does not have major conformational consequences, it induces in the latter conformational changes beyond the ones obtained with reduction.
Key Words:
Molecular Dynamics Simulations, Molecular Structure, Oxidation-Reduction,, cytochrome c3, redox-linked
