Main-chain complementarity in protein-protein recognition.
The existing theoretical approaches to protein-protein recognition concentrate on the details of the molecular surface at atomic resolution, while a possible role of the main chain in complex formation has been largely unexplored. To address this problem, we represented the molecules by C alpha atoms and applied the step-function potentials for intermolecular energy calculations. Since our goal was not to predict, as accurately as possible, the structure of a protein-ligand complex, but to reveal the role of the backbone in the formation of such a complex, all the potentials were identical and C alpha centered. Thus, for the specific purposes of our study, we do not simulate the difference in the side chains at the molecular surface. The structures were taken from known co-crystallized complexes. The intermolecular energy calculation was performed by a systematic 6-D search on a grid. The results revealed that in all cases tested (except antigen-antibody) the positions of the ligand at the binding site on the receptor corresponded to the lowest-energy configurations of the complex. The complementarity between the backbones, in general, may facilitate the initial placement of the ligand at the binding site of the receptor. At the same time, the identity and the specific conformation of the surface side chains play a crucial role in the next stage of the complex formation.
Vakser
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IA
Center for Molecular Design, Washington University, St Louis, MO 63130, USA.
D001665:Binding Sites; D006454:Hemoglobins / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D015202:Protein Engineering; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D006454:Hemoglobins; D008024:Ligands; D011506:Proteins