Binding free-energy landscapes of small molecule binder and non-binder to FMN riboswitch: All-atom molecular dynamics.

ABSTRACT: A small and flexible molecule, ribocil A (non-binder) or B (binder), binds to the deep pocket of the aptamer domain of the FMN riboswitch, which is an RNA molecule. This binding was studied by mD-VcMD, which is a generalized-ensemble simulation method. Ribocil A and B are structurally similar because they are optical isomers to each other. In the initial conformation of simulation, the ligands and the aptamer were completely dissociated in explicit solvent. The aptamer-ribocil B binding was stronger than the aptamer-ribocil A binding, which agrees with experiments. The computed free-energy landscape for the aptamer-ribocil B binding was funnel-like, whereas that for the aptamer-ribocil A binding was rugged. When passing through the gate (named "front gate") of the binding pocket, each liga

SUBMITTER: Higo J 

PROVIDER: S-EPMC10853809 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature