Review demonstrates the role of dynamic conformational ensembles in protein regulation, highlighting opportunities for novel allosteric therapeutics in oncology.
Key Points
To review the conceptual transition of protein allostery from static structural models to dynamic conformational ensembles and examine its utility in modern drug design.
Analyzed classical versus modern conceptual frameworks governing protein allosteric transitions and conformational dynamics.
Surveyed modern therapeutic applications targeting allosteric mechanisms across various disease pathways and oncogenic targets.
Dynamic conformational ensemble frameworks clarify how intrinsic structural fluctuations govern oncogenic mutations, molecular recognition, and protein folding.
Advances in conformational targeting have enabled novel modalities, including Cyclin E-CDK2 degrading PROTACs, the cyclophilin A-mediated pan-Ras glue daraxonrasib, and COP9 signalosome exosite modulators.