Effect of mutations on binding of ligands to guanine riboswitch probed by free energy perturbation and molecular dynamics simulations.

ABSTRACT: Riboswitches can regulate gene expression by direct and specific interactions with ligands and have recently attracted interest as potential drug targets for antibacterial. In this work, molecular dynamics (MD) simulations, free energy perturbation (FEP) and molecular mechanics generalized Born surface area (MM-GBSA) methods were integrated to probe the effect of mutations on the binding of ligands to guanine riboswitch (GR). The results not only show that binding free energies predicted by FEP and MM-GBSA obtain an excellent correlation, but also indicate that mutations involved in the current study can strengthen the binding affinity of ligands GR. Residue-based free energy decomposition was applied to compute ligand-nucleotide interactions and the results suggest that mutations highly a

SUBMITTER: Chen J 

PROVIDER: S-EPMC6649850 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature