Novel multi-objective affinity approach allows to identify pH-specific μ-opioid receptor agonists.

ABSTRACT: Opioids are essential pharmaceuticals due to their analgesic properties, however, lethal side effects, addiction, and opioid tolerance are extremely challenging. The development of novel molecules targeting the [Formula: see text]-opioid receptor (MOR) in inflamed, but not in healthy tissue, could significantly reduce these unwanted effects. Finding such novel molecules can be achieved by maximizing the binding affinity to the MOR at acidic pH while minimizing it at neutral pH, thus combining two conflicting objectives. Here, this multi-objective optimal affinity approach is presented, together with a virtual drug discovery pipeline for its practical implementation. When applied to finding pH-specific drug candidates, it combines protonation state-dependent structure and ligand preparation

SUBMITTER: Secker C 

PROVIDER: S-EPMC10510211 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature