Metformin Is a Direct SIRT1-Activating Compound: Computational Modeling and Experimental Validation.

ABSTRACT: Metformin has been proposed to operate as an agonist of SIRT1, a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase that mimics most of the metabolic responses to calorie restriction. Herein, we present an in silico analysis focusing on the molecular docking and dynamic simulation of the putative interactions between metformin and SIRT1. Using eight different crystal structures of human SIRT1 protein, our computational approach was able to delineate the putative binding modes of metformin to several pockets inside and outside the central deacetylase catalytic domain. First, metformin was predicted to interact with the very same allosteric site occupied by resveratrol and other sirtuin-activating compounds (STATCs) at the amino-terminal activation domain of SIR

SUBMITTER: Cuyas E 

PROVIDER: S-EPMC6232372 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature