Free-Energy Calculations for Bioisosteric Modifications of A₃ Adenosine Receptor Antagonists.

ABSTRACT: Adenosine receptors are a family of G protein-coupled receptors with increased attention as drug targets on different indications. We investigate the thermodynamics of ligand binding to the A₃ adenosine receptor subtype, focusing on a recently reported series of diarylacetamidopyridine inhibitors via molecular dynamics simulations. With a combined approach of thermodynamic integration and one-step perturbation, we characterize the impact of the charge distribution in a central heteroaromatic ring on the binding affinity prediction. Standard charge distributions according to the GROMOS force field yield values in good agreement with the experimental data and previous free energy calculations. Subsequently, we examine the thermodynamics of inhibitor binding in terms of the energet

SUBMITTER: Jandova Z 

PROVIDER: S-EPMC6679372 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature