Research

Kinetoplastid RNA Editing Ligase


Kinetoplastid RNA editing ligase (KREL) is an essential enzyme for trypanosoma brucei. T. brucei causes African sleeping sickness in humans. By characterizing the binding sites of KREL, we hope to find good drug targets that we can use to design pharmaceutical compounds to treat African sleeping sickness.

  1. We're currently creating molecular-modeling parameters for the nonstandard residues of the KREL protein. Once these parameters have been generated, we will use molecular modeling techniques to identify secondary binding sites that may make for good drug targets.

  2. We're currently doing a high-throughput computational screen to identify other proteins that have binding sites similar to that of KREL. By identifying these proteins, we hope to predict the side effects of our designed drugs. We also hope to predict other pathogenic proteins against which our newly-designed compounds may also be effective.

Matrix Metalloproteases


Matrix metalloproteases are enzymes responsible for cancer metastasis and inflammation in humans. Some pathogens, such as anthrax, also use matrix metalloproteases. By studying these proteins, we hope to develop drugs that will be effective in the treatment of cancer, chronic inflammation, and anthrax.

  1. We're currently doing a high-throughput computational screen of the MMP2 and MMP3 proteins. Once we've identified compounds that are strong selective inhibitors of MMP2, we'll improve their binding affinity using the LUDI algorithm. Because of our close collaboration with Dr. Seth Cohen, the compounds we identify can be quickly tested for their effectiveness against MMP2 and MMP3 in the chemistry lab.

  2. We're also performing a high-throughput computational screen of the anthrax lethal factor protein, also a matrix metalloprotease. Once we've identified compounds that are strong selective inhibitors of anthrax lethal factor, we'll likewise use the LUDI algorithm to find an improved drug inhibitor.

Accelerated Molecular Dynamics


Classical molecular dynamics simulations can take many weeks, even months, to complete. Because they are so computationally intensive, molecular dynamics simulations can simulate at most microsecond-long reactions. We're currently working on validating a new accelerated molecular dynamics technique that will overcome these time limitations.