We have used hydration free energies computed using quantum chemical methods as predictors of the reactivity of a variety of biologically active compounds. Our initial studies involved using the hydration energies of purine analogs as predictors of their proficiency as substrates for deaminase enzymes (e.g. ADAR2) studied by the Beal group at UC Davis. Subsequent studies have involved using the hydration energies of keto-amides present in drugs as predictors of whether or not they will form covalent adducts with their biological targets.
Wang, S. C.; Beal, P. A.; Tantillo, D. J. J. Comput. Chem. 2009, in press: "Covalent Hydration Energies for Purine Analogs by Quantum Chemical Methods"
Pokharel, S.; Jayalath, P.; Maydanovych, O.; Goodman, R.; Wang, S. C.; Tantillo, D. J.; Beal, P. A. J. Am. Chem. Soc. 2009, 131, 11882-11891: "Matching Active Site and Substrate Structures for an RNA Editing Reaction"
Henry B. Wedler, Christian S. Hamann, and Dean J. Tantillo: "TheTheoretical Hydration Energues of Biologically Relevant alpha-Ketoamides." Poster presented by Hoby Wedler at the SYLICCO.09 Symposium, Davis, CA, July 23, 2009.
