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

希尔赛尔MCB 98756891技术这项工作涉及一项研究和教育相结合的倡议，旨在开发基于结构的生物功能模型，这些模型可用作生物化学和细胞生物学实验室以及结构和生物物理实验室的研究工具。研究部分涉及基于系综的分子识别描述的开发和实验验证。这个计算模型将提供结构和能量之间的定量联系，将通过与实验确定的Src-Homology-3(SH3)结构域SEM5与其假定的多肽配体SOS的许多变体结合的热力学参数进行测试和改进。由此产生的基于系综的观点不仅应该提供亲和力的结构和热力学起源，还应该允许获得专一性的决定因素。由于该模型旨在用作推导假设、解释结果和指导研究工作的研究工具，该算法的所有元素都将编码到数学笔记本中，并可根据要求分发到UTMB内外配备适当设备的实验室。教育部分涉及在人类生物化学和遗传学系(HBC&AMP；G)开发以数学为基础的课程。除了共同制定以数学为基础的三门课程的教学大纲外，教育计划还围绕学生和教师的入门课程，向学生(和教师)传授将计算方法纳入他们自己的研究的各种策略。最近计算机技术的进步，加上生物数据库近乎指数级的增长，催生了快速增长的生物信息学领域。在这一新兴领域，无数的计算努力都集中在整合不同类型的数据来解决复杂的生物学问题上。事实上，这项工作就是这样的，研究工作的中心是整合结构数据库(例如蛋白质数据库)和热力学数据库，以推导分子识别、变构和信号转导的模型。在生物学这个新的计算时代，手头的任务不仅是开发方法本身，而且提供一种媒介，通过它这些方法可以在群体中传播，并提供在不同研究专业中结合这些方法的策略的途径。这一结合的研究和教育倡议的目标是通过开发有用的方法，实现方便和可访问的交互媒介(即数学)，促进这些计算方法的使用，并为学生和教职员工提供方法和媒介的培训。

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.