Identifying Functional Hotspot Residues for Biased Ligand Design in G-Protein-Coupled Receptors.

ABSTRACT: G-protein-coupled receptors (GPCRs) mediate multiple signaling pathways in the cell, depending on the agonist that activates the receptor and multiple cellular factors. Agonists that show higher potency to specific signaling pathways over others are known as "biased agonists" and have been shown to have better therapeutic index. Although biased agonists are desirable, their design poses several challenges to date. The number of assays to identify biased agonists seems expensive and tedious. Therefore, computational methods that can reliably calculate the possible bias of various ligands ahead of experiments and provide guidance, will be both cost and time effective. In this work, using the mechanism of allosteric communication from the extracellular region to the intracellular transducer p

SUBMITTER: Nivedha AK 

PROVIDER: S-EPMC5832328 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature