Impact of protein-ligand solvation and desolvation on transition state thermodynamic properties of adenosine A_2A ligand binding kinetics.

ABSTRACT: Ligand-protein binding kinetic rates are growing in importance as parameters to consider in drug discovery and lead optimization. In this study we analysed using surface plasmon resonance (SPR) the transition state (TS) properties of a set of six adenosine A_2A receptor inhibitors, belonging to both the xanthine and the triazolo-triazine scaffolds. SPR highlighted interesting differences among the ligands in the enthalpic and entropic components of the TS energy barriers for the binding and unbinding events. To better understand at a molecular level these differences, we developed suMetaD, a novel molecular dynamics (MD)-based approach combining supervised MD and metadynamics. This method allows simulation of the ligand unbinding and binding events. It also provides the system co

SUBMITTER: Deganutti G 

PROVIDER: S-EPMC5755719 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature