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John Stubbs, Ph.D., assistant professor of chemistry, and Amy Deveau, Ph.D., associate professor of chemistry and faculty member in the É«ÏãÊÓƵ Center for Excellence in the Neurosciences, published a research paper in the Journal of Chemical Information and Modeling in collaboration with alumnae Jennifer Bayron '10, a biochemistry and medical biology major.  The article is titled "Conformational Analysis of 6_- and 6_-Naltrexol and Derivatives and Relationship to Opioid Receptor Affinity" [J. Chem. Inf. Model. 2012, 52, 391_395].

The compounds studied are opioid receptor antagonists that were previously synthesized by É«ÏãÊÓƵ students and characterized in in vitro receptor assays at the National Institutes of Health.  The aim of the paper was to explore, using computational techniques, how low energy molecular conformations of naltrexol derivatives may correlate with binding preferences at opioid receptor subtypes.  The team made several conclusions.  First, they discovered that the boat conformer of Ring C is preferred over the chair in several circumstances.  Second, experimentally determined binding affinities for the 6_-Naltrexol series to the mu opioid receptor correlated directly with total energy difference.  And finally, the team found that compound binding affinity at the kappa opioid receptor increases as the aqueous solvation free energy of a given conformer increases.   When taken together, these findings help the team further delineate the structure-activity relationships for binding at the MOR and KOR, and provide further support that molecular polarity and conformation are key components to these relationships.