Application and Development of Molecular Dynamics Methods to Examine the Energy Landscapes of Protein Folding and Transient Protein -Protein Complexes

Abstract

A transient protein-protein complex of the photosynthetic reaction center and cytochrome c2 from Rhodobacter sphaeroides was studied using full-atom Steered Molecular Dynamics. Initial translation of cytochrome c2 at various heights over the surface of the reaction center revealed a probable exit pathway. Steered Molecular Dynamics was used to pull cyt c2 along the proposed pathway. Analysis of the non-bonded energies during the pull revealed reduction of attraction as the molecule moves toward the end of the reaction center. It was shown that the initial separation is due to disruption of electrostatic contacts by the water molecules. The cation-pi contact and the van der Waals interactions are the last to break. Computation of the docking free energy, by taking into the account the electrostatic, van der Waals, and entropic contributions, matched well with the experimental value. Extensive structure and sequence based evolutionary analyses of the cytochrome c2 revealed the conservation of certain contacts important for protein-protein interaction with a number of partners.