Conformational selection accelerates catalysis by an organocatalytic molecular motor
James Gallagher, Benjamin M. W. Roberts, Stefan Borsley, David A. Leigh
Abstract
Conformational dynamics are increasingly recognized as an important contributor to enzyme catalysis but are often overlooked in synthetic catalyst design. Here, we experimentally demonstrate faster catalysis by conformational selection caused by stochastic interconversion of two conformations of a catenane-based organocatalyst. The dependencies of the reaction rates on the relative positioning of the catalyst components during different stages of the catalytic cycle enable the dynamic organocatalyst to achieve order-of-magnitude rate accelerations over static or predominantly single-conformer analogs. The dynamic rate acceleration results in the emergent property of the organocatalyst acting as a directionally rotating motor. In demonstrating that conformational dynamics can overcome linear scaling relationships, these findings have implications for theories of enzyme catalysis and artificial catalyst design. The link between faster catalysis and directionally biased conformational dynamics may suggest that "motor molecules" could have first arisen in primitive form due to prebiotic evolutionary pressure to achieve faster catalysis.