Understanding the mechanisms underlying the catalytic properties of RNA have applications in the design of new biotechnology, and are also implicated in the evolutionary origins of life itself. Isotopic labels provide powerful and sensitive experimental probes to fingerprint the nature of transition states in biochemical reactions, which in turn can characterize different reaction mechanisms, particularly with the aid of first-principles calculations from fundamental physical laws in quantum mechanics.
In very recent paper, Prof. Darrin York and postdoctoral researcher Dr. Kin-Yiu Wong of Rutgers CCB and BioMaPS Institute, in collaboration with the experimental groups of Prof. Michael Harris at Case Western Reserve University and Prof. Joseph Piccirilli at the University of Chicago, researchers calculated primary and secondary kinetic isotope effects for a model compound which represents RNA cleavage transesterification with an ab initio path-integral method. The alignment of theory and experiment provided atomistic detail into the nature of the transition state, and the pathway and energy profile for the reaction of a both native, and thio-substituted systems
The paper has been featured in Angewandte Chemie (International Edition): [ URL: http://onlinelibrary.wiley.com/doi/10.1002/anie.201108319/abstract ] K.-Y. Wong, H. Gu, S. Zhang, J. A. Piccirilli, M. E. Harris, and D. M. York, Angew. Chem. Int. Ed. 2012, 51 (3), 647-651. DOI: 10.1002/anie.201104147 . [ URL: http://onlinelibrary.wiley.com/doi/10.1002/anie.201104147/abstract ]