Chandran, Vidya;Floeck, Dagmar;Helms, Volkhard - Protein-protein docking of cytochrome c2 to the bacterial reaction centre

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Title: Protein-protein docking of cytochrome c2 to the bacterial reaction centre	P21
Chandran, Vidya; Floeck, Dagmar; Helms, Volkhard vhelms@mpibp-frankfurt.mpg.de Max Planck Institute of Biophysics, Kennedyallee 70, 60596 Frankfurt, Germany

Predicting protein-protein interactions by computational docking to gain insight into the process of protein-protein recognition and study the energetics involved during these macromolecular associations are gaining great importance in structural bioinformatics and biophysics. As a model system, we investigated by computational docking, the binding of cytochrome c2 in bound and free conformations to its physiological partner, photosynthetic reaction centre (RC), in its free conformation both from Rhodobacter sphaeroides. Initial docking was done using the program FTDOCK (Gabb & Sternberg, 1998) and the resultant complexes were then filtered using biological information. Further structural and energetic refinement of side chain positions was performed using the program MULTIDOCK (Jackson et. al., 1998). To allow reliable comparison of the complexes on energetic terms, the complexes filtered by FTDOCK and also the complexes refined by MULTIDOCK were optimised by rigid-body energy minimization with the molecular mechanics package CHARMM and electrostatic binding energies were computed using the Poisson-Boltzmann solver UHBD. These docked structures were compared to a recent crystal structure of the complex (Axelrod et al., 2002) using measures of RMSD and Percentage of Native Contacts (PNC). Comparison to the crystal structure resulted in 4/6 complexes filtered out for the bound conformation and 5/12 complexes filtered out for the free conformation of cyt c2 (finer docking done to extract more complexes) within 2.5 A RMSD and more than 75% PNC. As expected, the RMSD of docked complexes involving the bound conformation of cyt c2 with respect to the crystal complex was smaller than for complexes involving cyt c2 in its free conformation. The energy landscape of complex formation was characterized by comparing the docked complexes of cytochrome c2 with RC to the experimental crystal structure of the complex. Again, docked complexes using the bound conformation of cyt c2 had lower energies than those using the free conformation of cyt c2. The total energies computed for multiple predicted complexes docked using the bound conformation of cyt c2 were of similar magnitude and 2-6 kcal/mol lower than the total energy for the crystal complex. These findings agree with experimental observations of multiple, possibly transient binding modes of cytochrome c2 to RC allowing productive electron transfer from a variety of binding positions.