ИСТИНА

Transient protein-protein complexes play an important role in various processes in the living cell: activation and inhibition of enzyme activity, reception and transfer of information, redox reactions and other. This work is devoted to reconstruction of plastocyanin – cytochrome f complex formation. We simulated the sequence of events at diffusion encounter of the proteins by Brownian and molecular dynamics methods and revealed possible intermediate steps by cluster analysis. The method of Brownian dynamics was used to simulate diffusion of proteins, their approaching each other and subsequent formation of encounter complexes with account of electrostatic interactions in a rigid body approximation [1]. Full atom explicit solvent molecular dynamics [2] with OPLS-AA force field [3] was then used to simulate further protein converging and transformation of the encounter complexes into final complexes with account of conformational flexibility of protein molecules. We obtained many various electrostatically favorable positions of the proteins with respect to each other corresponding to the state of diffusion entrapment by rigid body Brownian dynamics, and calculated the most typical structures of such complexes by hierarchical cluster analysis. This let us suggest the sequence of events preceding formation of the final functional complex. Further simulation by all-atom molecular dynamics with explicit solvent helped to reveal the intermediate states in the process of protein-protein complex formation and reconstruct the process of transformation of these states into the final complex.