Discovery of cryptic allosteric sites using reversed allosteric communication by a combined computational and experimental strategy
Duan Ni, Jiacheng Wei, Xinheng He, Ashfaq Ur Rehman, Xinyi Li, Yuran Qiu, Jun Pu, Shaoyong Lu, Jian Zhang
Abstract
)-dependent protein lysine deacetylase sirtuin 6 (Sirt6). A potential novel cryptic allosteric site located around the L116, R119, and S120 residues within the dynamic ensemble of Sirt6 was identified. The allosteric effect of the predicted site was further quantified and validated using both computational and experimental approaches. This study proposed a state-of-the-art computational pipeline for detecting allosteric sites based on reversed allosteric communication. This method enabled the identification of a previously uncharacterized potential cryptic allosteric site on Sirt6, which provides a starting point for allosteric drug design that can aid the identification of candidate pockets in other therapeutic targets.