Research

Allostery plays a critical role in many biological processes, most prominently in signal transduction, transcriptional control, and metabolism. Allosteric regulation of enzymes, for example, provide one of the most direct and rapid means of modifying small molecule concentrations in cells. Given its inherently cryptic nature, enzyme allostery is likely more prevalent than currently understood. On one side, our research focuses on the phenomenon of enzyme allostery itself. The long-term goals here are:

i) to identify allosterically regulated enzymes and their intrinsic effectors

ii) to elucidate the molecular forces and mechanisms at work

iii) to explore the biological significance of these mechanisms

Another pillar of our research entails pharmacological application of enzyme allostery. Targeting allosteric mechanisms has attracted significant attention as an emerging basis of drug discovery. Allosteric effectors offer a number of advantages as drugs, including selectivity towards specific homologs, additivity or synergy with orthosteric drugs, and opportunities for tunable biological effects. The research objectives here are shorter-term and enzyme-specific, but generally include:

i) identification of allosteric inhibitors by virtual and/or in vitro screening

ii) characterization of enzyme-inhibitor binding

iii) confirmation of biological effects in cell-based/pre-clinical models