Protein–protein docking of electron transfer complexes: Cytochrome c oxidase and cytochrome c

Electron transferring protein complexes form only transiently and the crystal structures of electron transfer protein–protein complexes involving cytochrome c could so far be determined only for the pairs of yeast cytochrome c peroxidase (CcP) with iso‐1‐cytochrome c (iso‐1‐cyt c ) and with horse heart cytochrome c (cyt c ). This article presents models from computational docking for complexes of cytochrome c oxidase (COX) from Paracoccus denitrificans with horse heart cytochrome c , and with its physiological counterpart cytochrome c 552 ( c 552). Initial docking is performed with the FTDOCK program, which permits an exhaustive search of translational and rotational space. A filtering procedure is then applied to reduce the number of complexes to a manageable number. In a final step of structural and energetic refinement, the complexes are optimized by rigid‐body energy minimization with the molecular mechanics package CHARMM. This methodology was first tested on the CcP:iso‐1‐cyt c complex, in which the complex with the lowest CHARMM energy has an RMSD from the crystal structure of only 1.8 Å (C α carbon atoms). Notably, the crystal conformation has an even lower energy. The same procedure was then applied to COX:cyt c and COX: c 552. The lowest‐energy COX:cyt c complex is very similar to a docking model previously described for the complex of bovine cytochrome c oxidase with horse heart cytochrome c . For the COX: c 552 complex, cytochrome c 552 is found in two different orientations, depending on whether it is docked against COX from a two‐subunit or from a four‐subunit crystal structure, respectively. Both conformations are discussed critically in the light of the available experimental data. Proteins 2002;47:75–85. © 2002 Wiley‐Liss, Inc.