Structural insights from an in silico molecular docking simulation of complement component 3a receptor 1 with an antagonist.

Complement component 3a receptor 1 (C3aR) is an anaphylatoxin receptor that mediates inflammatory processes. Although considerable effort has gone into discovering the antagonists and agonists of C3aR, structural insights are required to search for effective ligands and to elucidate their binding modes and the mechanism of activation and inactivation. No experimental structural data of C3aR have yet been reported. We investigated the binding mode of an antagonist of C3aR using a combination of homology modeling, ligand docking, molecular dynamics simulations, and binding free energy calculations. We produced a plausible binding model consistent with the reported experimental data. We believe that this model is appropriate for the identification of new C3aR antagonists, as it can distinguish between antagonists and decoy compounds.