We use theoretical and computational techniques to help solve biological and medical problems. Our current research topics can be grouped into four categories: Gene discovery. We analyze the Expressed Sequence Tag (EST) DNA sequence database to discover genes that are specifically expressed in a particular organ or tumor. The products of such genes can potentially be used as targets for delivery of antitumor agents, for anticancer vaccine development, and for tumor imaging. This is a collaboration with Dr. Ira Pastan's Molecular Biology Section. Immunotoxins. Immunotoxins are man-made molecules constructed by joining an anti-cancer antibody and a suitable toxin, in our case, the pseudomonas exotoxin A. Ideally, these molecules will bind only to the target cancer cells and kill them. There are many such designed molecules, each having a specific antibody for a particular cancer. Some of these molecules, made by Dr. Pastan's laboratory, produced highly encouraging results during the phase I clinical trials. We study these molecules and design mutations that will alter/improve their properties as an effective drug. This is also a collaborative work with Dr. Pastan's laboratory. Protein structure. We study the protein structures and the problem of classifying all protein structures. Currently, we are working on (1) improving our automatic protein structure alignment/search algorithm; (2) comparing the results of two very different such algorithms to the manually procured world-standard protein classification database, SCOP; (3) developing context specific score matrices to be used to recognize protein sequences that bear remote homology to a protein of known structure; and (4) improving the sensitivity of a sequence alignment algorithm that does not use a gap penalty. We also occasionally collaborate with other scientists on protein structure modeling projects. Hydrophobicity. We study the phenomenon of hydrophobicity by means of statistical thermodynamics. The hydrophobic effect is believed to be one of the main forces that determine the structure, stability, and interaction of protein and other biologically important molecules. For more information on our research and on the software that we developed, please check our other website http://lmbbi.nci.nih.gov/
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