The Molecular Modeling Section uses and develops theoretical tools to study and predict the structure and stability of globular protein molecules and to design protein molecules with new or improved properties. Following are some of the research activities and results that we obtained during this reporting period: (1) The in-house molecular graphics program, GEMM, is being modified in order to use the open GL graphics library. This modification will make the program run faster on modern workstations. (2) A new protein structure prediction method was devised that uses a discrete set of states and a hierarchical search procedure. The work is only at the beginning stage, but preliminary results are highly encouraging. (3) A new fast procedure was developed for making protein structure comparisons. Because the procedure is fast, we could compare all known protein structures with all others and cluster them into structurally homologous protein groups. The results are being analyzed currently. (4) In collaboration with the Molecular Biology Section, we (a) designed mutations to increase the stability and binding properties of a number of tumor-specific antibodies, (b) designed mutations to reduce the liver toxicity of an immunotoxin, (c) designed a new single-chain Fv molecule by base loop exchange and sequence permutation, and (d) designed peptide linkers for an MHC molecule and a peptide from gp100 so that the ternary complex can be expressed as a single-chain molecule. (5) By analyzing the expressed sequence tag (EST) database, we identified three previously uncharacterized genes specifically expressed in the human prostate but not in other organs. We are working to identify other such genes, and in collaboration with the Molecular Biology Section, characterizing the genes and the gene products.
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