CAREER: An Integrated Research and Education Program for the Development and Use of Computational Approaches in Biological Studies

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HilserMCB 98756891. TechnicalThis work involves a combined research and education initiative aimed atthe development of structure-based models of biological function, which canbe used as research tools in biochemistry and cell biology labs as well asin structural and biophysical labs. The research component involves thedevelopment and experimental validation of an ensemble-based description ofmolecular recognition. This computational model, which will provide aquantitative link between structure and energy, will be tested and refinedby comparison to the experimentally determined thermodynamic parameters forthe binding of the Src-homology-3 (SH3) domain SEM5 with numerous variantsof its putative peptide ligand, Sos. The resultant ensemble-based viewshould not only provide the structural and thermodynamic origins of theaffinity, it should allow access to the determinants of specificity aswell. As the model is intended to be used as a research tool for derivinghypothesis, interpreting results, and directing research efforts, allelements of this algorithm will be coded into Mathematica notebooks whichcan be distributed upon request to suitably equipped labs both within UTMBand outside of the University. The education component involves developinga Mathematica-based curriculum in the Department of Human BiologicalChemistry and Genetics (HBC&G). In addition to the co-development of aMathematica -based syllabus for three courses, the education plan centersaround introductory courses for students and faculty, wherein students (andfaculty) are taught various strategies for incorporating computationalapproaches in their own research.2. Non-technicalRecent advances in computer technology, coupled to the near exponentialgrowth of biological databases have spawned the rapidly growing field ofbioinformatics. From within this emerging field, numerous computationalefforts have focused on integrating different types of data in tacklingcomplex biological problems. Indeed, such is the case in this work, whereresearch efforts are centered on integrating the structural (e.g. ProteinData Bank) and thermodynamic databases to derive models for molecularrecognition, allosterism, and signal transduction. The task at hand inthis new computational era in biology is not only to develop the methodsthemselves, but to provide a medium through which these methods can bedisseminated among groups, and to provide access to strategies forincorporating these methods in a diverse array of research specialties.The goal of this combined research and education initiative is to promotethe use of these computational approaches by developing useful methods,implementing a convenient and accessible medium of interaction (i.e.Mathematica ), and providing students and faculty with training in both themethods and the medium.