High-resolution deep mutational scanning of the melanocortin-4 receptor enables target characterization for drug discovery.

ABSTRACT: Deep Mutational Scanning (DMS) is an emerging method to systematically test the functional consequences of thousands of sequence changes to a protein target in a single experiment. Because of its utility in interpreting both human variant effects and protein structure-function relationships, it holds substantial promise to improve drug discovery and clinical development. However, applications in this domain require improved experimental and analytical methods. To address this need, we report novel DMS methods to precisely and quantitatively interrogate disease-relevant mechanisms, protein-ligand interactions, and assess predicted response to drug treatment. Using these methods, we performed a DMS of the melanocortin-4 receptor (MC4R), a G-protein-coupled receptor (GPCR) implicated in obesi

SUBMITTER: Howard CJ 

PROVIDER: S-EPMC11981609 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature