Demystifying P2Y₁ Receptor Ligand Recognition through Docking and Molecular Dynamics Analyses.

ABSTRACT: We performed a molecular modeling analysis of 100 nucleotide-like bisphosphates and 46 non-nucleotide arylurea derivatives previously reported as P2Y₁R binders using the recently solved hP2Y₁R structures. We initially docked the compounds at the X-ray structures and identified the binding modes of representative compounds highlighting key patterns in the structure-activity relationship (SAR). We subsequently subjected receptor complexes with selected key agonists (2MeSADP and MRS2268) and antagonists (MRS2500 and BPTU) to membrane molecular dynamics (MD) simulations (at least 200 ns run in triplicate, simulation time 0.6-1.6 μs per ligand system) while considering alternative protonation states of nucleotides. Comparing the temporal evolution of the ligand-protein int

SUBMITTER: Ciancetta A 

PROVIDER: S-EPMC5953180 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature