Computational Investigation of Structural Basis for Enhanced Binding of Isoflavone Analogues with Mitochondrial Aldehyde Dehydrogenase.

ABSTRACT: Isoflavone compounds are potent inhibitors against mitochondrial aldehyde dehydrogenase (ALDH2) for the treatment of alcoholism and drug addiction, and an in-depth understanding of the underlying structural basis helps design new inhibitors for enhanced binding. Here, we investigated the binding poses and strengths of eight isoflavone analogues (including CVT-10216 and daidzin) with ALDH2 via computational methods of molecular docking, molecular dynamics (MD) simulation, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), steered MD, and umbrella sampling. Neither the Vina scoring of docked and MD-sampled complexes nor the nonbonded protein-inhibitor interaction energy from MD simulations is able to reproduce the relative binding strength of the inhibitors compared to experimenta

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC8908493 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature