New paradigm of q-CAR drug development targeting disease-specific protein conformations.

Drug discovery has progressed to using advanced AI-driven platforms. These systems rely heavily on static structures and overlook an essential aspect: protein motion-conformational transitions and local fluctuations-is essential for function, as "no motion, no function." Thus, this review discusses recent progress in measuring protein conformations and dynamics and introduces a new concept, "quantitative conformation-activity relationship (q-CAR)," aimed at developing drugs that target disease-specific protein conformations in the future.