Supervised Molecular Dynamics (SuMD) as a Helpful Tool To Depict GPCR-Ligand Recognition Pathway in a Nanosecond Time Scale

Supervised MD (SuMD) is a computational method that allows the exploration of ligand-receptor recognition pathway investigations in a nanosecond (ns) time scale. It consists of the incorporation of a tabu-like supervision algorithm on the ligand-receptor approaching distance into a classic molecular dynamics (MD) simulation technique. In addition to speeding up the acquisition of the ligand-receptor trajectory, this implementation facilitates the characterization of multiple binding events (such as meta-binding, allosteric, and orthosteric sites) by taking advantage of the all-atom MD simulations accuracy of a GPCR-ligand complex embedded into explicit lipid-water environment.