Research in my laboratory is concerned with the discovery and design of small molecules that alter cellular processes both in vitro and in vivo with the aim of identifying agents that can be used in the clinic for the treatment of disease. To that end, we specialize in the use and development of computational techniques that are implemented on large supercomputers for the discovery of lead molecules and their optimization. The discovery of leads is accomplished through the screening of libraries containing millions of compounds. We use biochemical and biophysical techniques to validate these hits against the target of interest; these include fluorescence spectroscopy, surface plasmon resonance, and isothermal titration calorimetry. The potency and the pharmacokinetic properties of lead compounds are then optimized through structure-based and computer-aided chemical synthesis both in our laboratory and through collaborative efforts. Computational tools in conjunction with data from NMR spectroscopy and crystallography are used to characterize the three dimensional structure of the compounds bound to their receptor, as well as the motion that these systems experience. These studies play an important role in guiding our lead optimization efforts as well as in enabling us to gain a deeper understanding of the fundamental processes that guide molecular recognition in biological systems. We are particularly interested in cell surface receptors that are implicated in various cancers and bacterial infection in Staphylococcus aureus. The ability of compounds to prevent cancer cell growth, invasion, metastasis, as well as their impact on various cellular pathways is assessed through various cell-based studies that are conducted in our laboratory. In vivo studies are carried out through collaborations with investigators in the IU School of Medicine.
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