The Molecular Modeling Section develops and uses theoretical tools to study and predict the structure and stability of globular protein molecules and to design protein molecules with new or improved properties. It also analyzes the Expressed Sequence Tag (EST) cDNA database to discover new genes for use as targets for immunotoxins in cancer therapy. Some of the notable achievements made during this reporting period are: (a) A new fast procedure has been developed for making protein structure comparisons. The method can be used to obtain an overall view of all known protein fold types and to study the structural relationship between any two proteins that are remotely related evolutionarily. (b) A new measure was devised for scoring the fitness between a protein sequence and any known three-dimensional protein structure. The new scoring scheme can be used to improve fold prediction of a protein structure when only its sequence is known. (c) A new ab initio protein structure search engine was designed and partially developed. It uses novel procedures (window growth, evolutinary algorithm, and efficient local moves), which make it particularly efficient.(d) Simple procedures have been designed for finding mutations that will increase the stability or reduce non- specific toxicity of single chain antibody Fv domains. The procedures were proven to be effective by experimental tests using immunotoxins made of several different antibody Fv domains.(e) Found several new members of the GAGE family of tumor antigens by EST analysis. (f) Found that prostate epithelium cells express a truncated version of the TCRg gene. - immunotoxin, protein engineering, protein folding, protein stability, protein structure, bioinformatics, - Neither Human Subjects nor Human Tissues
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