MD simulation of the adsorption process of Cytochrome C on Self Assembled Monolayers

DAMIÁN J. ÁLVAREZ PAGGI; DIEGO F. MARTIN,; DANIEL MURGIDA; MARCELO A. MARTI

Montevideo-Uruguay

Congreso; International Conference Biological Physics (ICBP); 2007

IUPAB-SAB

Most of the natural reactions of redox proteins occur at or in membranes in a completely different chemical environment as that found in solution. Electrochemical and spectroscopic studies of these proteins are therefore performed with the protein immobilized on a self assembled monolayer (SAM) on electrodes. Many studies of this kind have been performed for cytochrome c (Cyt C) adsorbed on carboxyl terminated SAMs. A key issue for interpreting these results from a microscopic point of view is the knowledge of the atomistic structure of the SAM-protein complex. However, although the protein structure in solution and the SAM structure may be known, no experimental technique allows the determination of the complex structure. An unknown and most relevant parameter is the relative orientation of the protein to the monolayer. Molecular dynamics (MD) simulations are an excellent option to study the structure and dynamics of biomolecules in solution and at membranes. In this work we have analyzed the relevant conformations of Cyt C adsorbed on carboxyl terminated SAMs using Multiple Steered MD (MSMD). The MSMD technique, using Jarzinsky´s inequality, allowed us to determine the relevant complex structures (i.e. those with higher binding energy), and study the binding process.  Moreover, by varying the net charge of the SAMs the effect of the electric field on protein binding and mobility can be studied. Last, but not least, the rate constant for electron transfer (ket) was estimated for the low energy structures obtained using the pathways algorithm. Comparison of the ket values between different structures allowed us to study the role of protein conformation and estimate the key residues involved in the electron transfer process.