Protein–protein docking of electron transfer complexes: Cytochromecoxidase and cytochromec

Electron transferring protein complexes form only transiently and the crystal structures of electron transfer protein–protein complexes involving cytochromeccould so far be determined only for the pairs of yeast cytochromecperoxidase (CcP) with iso‐1‐cytochromec(iso‐1‐cytc) and with horse heart cytochromec(cytc). This article presents models from computational docking for complexes of cytochromecoxidase (COX) fromParacoccus denitrificanswith horse heart cytochromec, and with its physiological counterpart cytochromec552 (c552). 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‐cytccomplex, in which the complex with the lowest CHARMM energy has an RMSD from the crystal structure of only 1.8 Å (Cαcarbon atoms). Notably, the crystal conformation has an even lower energy. The same procedure was then applied to COX:cytcand COX:c552. The lowest‐energy COX:cytccomplex is very similar to a docking model previously described for the complex of bovine cytochromecoxidase with horse heart cytochromec. For the COX:c552 complex, cytochromec552 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.