Conformational ensembles in drug discovery
Proteins are not rigid structures; they consist of dynamic ensembles. Drugs whose protocols target ensembles are expected to have higher efficacy.
In this review, the authors explain the profound roles and merits of conformational ensembles in drug discovery and why targeting them is expected to have higher efficacy.
Drugs that target ensembles can cooperatively extend residence times and specificity of both orthosteric and allosteric drugs.
Sampling of ensembles can capture cryptic pockets, including exosites. Exosites, which adjoin ATP or active sites, are especially coveted drug targets with the strongest cooperativity.
Learning oncogenic protein mechanisms is essential for successful design protocols. It provides insights and can help in pioneering drug discovery.
https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(26)00006-4
