Structural biology of chemokine and chemokine receptors, inflammation, and protein therapeutics.

Our laboratory is interested in exploiting the structural elements of proteins for rational drug design. Chemokines, a large family of cytokines, have gained tremendous attention in recent years for their role in immune and inflammation related processes, HIV infection, metastasis, and organogenesis.They mediate their function by binding to G-protein coupled 7-TM receptors on leukocytes. We are interested in understanding the molecular basis of ligand-receptor interaction. Knowledge of the structure, dynamics, and thermodynamics of the ligand in the free and the receptor-bound form is essential to accomplish this goal.It is now possible to determine structures of proteins and protein-receptor complexes beyond 20 to 30 kDa due to advances in NMR methodology and availability of high field spectrometers. We will use a variety of multinuclear and multidimensional NMR techniques in conjunction with protein engineering and molecular modeling.These studies will form the foundation for designing lead compounds that could function as drugs for diseases such as cancer, heart diseases, and AIDS.

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