Discovery of Potent and Selective CB2 Agonists Utilizing a Function-Based Computational Screening Protocol.

ABSTRACT: Nowadays, the identification of agonists and antagonists represents a great challenge in computer-aided drug design. In this work, we developed a computational protocol enabling us to design/screen novel chemicals that are likely to serve as selective CB2 agonists. The principle of this protocol is that by calculating the ligand-residue interaction profile (LRIP) of a ligand binding to a specific target, the agonist-antagonist function of a compound is then able to be determined after statistical analysis and free energy calculations. This computational protocol was successfully applied in CB2 agonist development starting from a lead compound, and a success rate of 70% was achieved. The functions of the synthesized derivatives were determined by in vitro functional assays. Moreover, the id

SUBMITTER: Ge H 

PROVIDER: S-EPMC10623575 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature