Docking and molecular dynamics simulation of the Azurin-Cytochrome c551 electron transfer complex

We coupled protein-protein docking procedure with molecular dynamics (MD) simulation to investigate the electron transfer (ET) complex Azurin-Cytochrome c551 whose transient character makes difficult a direct experimental investigation. The ensemble of complexes generated by the docking algorithm are filtered according to both the distance between the metal ions in the redox centres of the two proteins and to the involvement of suitable residues at the interface. The resulting best complex (BC) is characterized by a distance of 1.59 nm and involves Val23 and Ile59 of Cytochrome c551. The ET properties have been evaluated in the framework of the Pathways model and compared with experimental data. A 60 ns long MD simulation, carried on at full hydration, evidenced that the two protein molecules retain their mutual spatial positions upon forming the complex. An analysis of the ET properties of the complex, monitored at regular time intervals, has revealed that several different ET paths are possible, with the occasional intervening of water molecules. Furthermore, the temporal evolution of the geometric distance between the two redox centres is characterized by very fast fluctuations around an average value of 1.6 nm, with periodic jumps at 2nm with a frequency of about 70 MHz. Such a behaviour is discussed in connection with a nonlinear dynamics of protein systems and its possible implications in the ET process are explored. Copyright (c) 2007 John Wiley & Sons, Ltd.