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

HilserMCB 98756891。技术这项工作涉及一个联合的研究和教育计划，旨在开发基于结构的生物功能模型，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。 研究部分涉及开发和实验验证的一个整体为基础的描述分子识别。 这个计算模型，这将提供一个定量的结构和能量之间的联系，将进行测试和refinedby比较实验确定的热力学参数为结合的Src同源性3（SH3）结构域SEM5与众多的变体，其推定的肽配体，Sos。 由此产生的基于整体的观点不仅应该提供亲和性的结构和热力学起源，还应该允许获得特异性的决定因素。 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，因此该算法的所有元素将被编码到Mathematica笔记本中，该笔记本可根据要求分发给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 G）开发基于数学的课程。 除了为三门课程共同开发基于Mathematica的教学大纲外，教育计划还围绕着学生和教师的入门课程，其中学生（和教师）被教导在自己的研究中融入计算方法的各种策略。非技术性计算机技术的最新进展，加上生物数据库的指数级增长，催生了生物信息学的快速发展。 在这个新兴的领域中，许多计算工作都集中在整合不同类型的数据来解决复杂的生物问题。 事实上，这是在这项工作的情况下，研究工作集中在整合结构（如蛋白质数据库）和热力学数据库，以获得分子识别，变构和信号转导模型。 在这个生物学的新计算时代，我们的任务不仅是发展这些方法本身，而且要提供一个媒介，通过它这些方法可以在群体之间传播，并提供将这些方法纳入各种研究专业的策略。这项研究和教育联合倡议的目标是通过发展有用的方法来促进这些计算方法的使用，实施一个方便和可访问的交互媒介（即Mathematica），并为学生和教师提供方法和媒介方面的培训。

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.