In binding to ligands (bind), biological systems undergo a conformational change (conf) whereby their specificity and affinity become finely tuned. As a principal part of allostery (‘second secret of life’), the coupling of conf and bind processes enables the emergence of complex multivalent systems with intriguing mechanisms of action. Two limiting mechanisms have been identified for describing the order by which conf and bind take place. Conformational selection (CS) postulates that a receptor exists as an ensemble of interconvertible conformations from which only the optimal conformer gets selected for binding to a ligand. Induced fit (IF) asserts that non-optimal conformer of the receptor gets associated with the ligand, which then induces 3D reshaping of a receptor into the conformation that is most complementary to the ligand. As CS and IF have often been viewed as mutually exclusive, we wondered about their simultaneous occurrence in an abiotic system. Using experimental (i.e. X-ray, solution NMR) and computational (DFT, MD, ASMD) techniques we extracted structural details of interchanging conformational states (free and bound) characterizing the complexation of small molecules by molecular baskets. Next, we characterized dynamics of the basic (conf and bind) chemical steps to reveal the participation of both CS and IF by which our baskets operate. In my talk, I plan to describe computational and experimental methods for elucidating mechanistic details by which molecular recognition take place in abiotic systems. A goal is to aid the design of novel supramolecular systems capable of performing increasingly demanding tasks and self-regulation, but also assists us in understanding complex biological processes and their regulatory features.

Conformational selection and induced fit in abiotic systems

ACS Spring 2022

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