What We Do

Computational Translational Research

With petascale computing power on the immediate horizon and exascale computing not far behind, computational studies have the opportunity to make unprecedented contributions to drug discovery efforts. Large-scale simulations of increasingly realistic biological systems will allow us to investigate protein function and molecular recognition in atomic detail. These investigations will help drive discovery efforts and experimental work on these systems in collaboration with leading experimentalists. Our current investigations concern the neglected tropical diseases borne by the trypanosome organisms, potentially pandemic avian influenza, cancer, Chlamydia, and the cytochrome P450s.

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Addressing Complexity in Molecular Recognition

The current model for computer-aided drug design is simply to take one or a few crystallographic structure(s) of a protein receptor and design a single molecule to block its activity. Though this model has had some success, more sophisticated drug discovery and design methodologies will significantly increase the chances of scientists being able to design more effective drugs faster. Our work in this area focuses primarily on three major goals: the incorporation of receptor flexibility, investigating mechanisms of drug and antiviral resistance, and disease network pharmacology.

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Multiscale Control Mechanisms in Nitrogen Metabolism

Central to understanding the complex inner-workings of the cell will be expanding our knowledge of the cellular machinery driving the vast assembly of processes that sustain life. The major workhorses of the cell are molecular machines known as enzymes. Our research aims to add insight into the many unanswered questions about their function. Two particularly intriguing questions are: how do enzymes communicate information between remote sites in the protein (a process known as allosteric regulation), and what are the mechanisms proteins employ to transport metabolic intermediates via substrate channeling?