UKRI/BBSRC-NSF/BIO: Evolving quantum mechanical tunnelling in enzymes

Enzymes are the most effective catalysts on the planet. They have the capability of speeding chemical reactions by a factor of up to 1015 over uncatalyzed reactions. Amazingly, after decades of research, the way this occurs is still in many instances a mystery to chemists and biologists. In addition, while chemistry is governed by the laws of Quantum Mechanics, there is still controversy over the importance of quantum mechanical effects in enzymatic reactions. The use of quantum principles would potentially allow many technological advances such as creating bio-inspired catalysts that were immune to low temperatures and have broader reactivities. This project explores the way such quantum effects may be built into enzyme function using the technology known as directed evolution. A Nobel prize winning technology that allows scientists to create enzyme functions in the laboratory using evolutionary principles in months rather than millennia. This project will train pre-and post-doctoral students in interdisciplinary research and broaden their experience by exposing them to international research collaboration. The functions of enzymes remain a topic of hot debate in the scientific community. Two of the most important areas of controversy are the importance of the coupling of dynamics to enzyme function, and what that has to do with the importance of quantum effects such as tunneling on enzyme rate. This project explores such question through the application of rare event sampling for enzymatic chemistry. The PI has pioneered such studies in particular the use of Transition Path Sampling coupled with committor distribution analysis to identify rigorous reaction coordinates. The PI has also developed methods to include quantum dynamics via path integral simulations. These will be coupled with directed evolution experiments of with UK collaborators who in their projects will craft artificial enzymes optimized for example to transfer deuterons rather than protons. These experiments coupled with the project described will show if quantum capabilities can be built into artificial enzymes, and just what those capabilities will allow. This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council where NSF funds the US investigator and BBSRC funds the UK partner. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.