Use of pair potentials across protein interfaces in screening predicted docked complexes

✍ Scribed by Gidon Moont; Henry A. Gabb; Michael J.E. Sternberg

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 100 KB
• Volume: 35
• Category: Article
• ISSN: 0887-3585
• DOI: 10.1002/(sici)1097-0134(19990515)35:3<364::aid-prot11>3.0.co;2-4

✦ Synopsis

Empirical residue-residue pair potentials are used to screen possible complexes for protein-protein dockings. A correct docking is defined as a complex with not more than 2.5 Å rootmean-square distance from the known experimental structure. The complexes were generated by ''ftdock'' (Gabb et al. J Mol Biol 1997;272:106-120) that ranks using shape complementarity. The complexes studied were 5 enzyme-inhibitors and 2 antibody-antigens, starting from the unbound crystallographic coordinates, with a further 2 antibodyantigens where the antibody was from the bound crystallographic complex. The pair potential functions tested were derived both from observed intramolecular pairings in a database of nonhomologous protein domains, and from observed intermolecular pairings across the interfaces in sets of nonhomologous heterodimers and homodimers. Out of various alternate strategies, we found the optimal method used a mole-fraction calculated random model from the intramolecular pairings. For all the systems, a correct docking was placed within the top 12% of the pair potential score ranked complexes. A combined strategy was developed that incorporated ''multidock,'' a side-chain refinement algorithm (Jackson et al.