Similarities between the Binding Sites of SB-206553 at Serotonin Type 2 and Alpha7 Acetylcholine Nicotinic Receptors: Rationale for Its Polypharmacological Profile

摘要: Evidence from systems biology indicates that promiscuous drugs, i.e. those act simultaneously at various protein targets, are clinically better in terms of efficacy, than a more selective fashion. This has generated new trend drug development called polypharmacology. However, the rational design compounds is difficult task, particularly when drugs aimed to receptors with diverse structure, function and endogenous ligand. In present work, using docking molecular dynamics methodologies, we established most probable binding sites SB-206553, originally described as competitive antagonist serotonin type 2B/2C metabotropic (5-HT2B/2CRs) recently positive allosteric modulator ionotropic α7 nicotinic acetylcholine receptor (nAChR). To this end, employed crystal structures 5-HT2BR templates build homology models 5-HT2CR nAChR, respectively. Then, statistical algorithm, similarity between these was determined. Our analysis showed plausible for SB-206553 5-HT2Rs nAChR remarkably similar, both size chemical nature amino acid residues lining pockets, thus providing rationale explain its affinity towards types. Finally, computational tool multiple site alignment, determined consensus site, which should be useful novel acting two types highly different targets.