Computational Study for the Unbinding Routes of β-N-Acetyl-d-Hexosaminidase Inhibitor: Insight from Steered Molecular Dynamics Simulations.

ABSTRACT: β-N-Acetyl-d-hexosaminidase from Ostrinia furnacalis (OfHex1) is a new target for the design of insecticides. Although some of its inhibitors have been found, there is still no commercial drug available at present. The residence time of the ligand may be important for its pharmacodynamic effect. However, the unbinding routes of ligands from OfHex1 still remain largely unexplored. In the present study, we first simulated the six dissociation routes of N,N,N-trimethyl-d-glucosamine-chitotriomycin (TMG-chitotriomycin, a highly selective inhibitor of OfHex1) from the active pocket of OfHex1 by steered molecular dynamics simulations. By comparing the potential of mean forces (PMFs) of six routes, Route 1 was considered as the most possible route

SUBMITTER: Hu S 

PROVIDER: S-EPMC6471479 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature