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

HilserMCB 98756891。技术：这项工作包括研究和教育的结合，旨在开发基于结构的生物功能模型，这些模型可以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。研究部分包括基于分子识别的集成描述的开发和实验验证。该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 - homological -3 （SH3）结构域SEM5与其假定的肽配体so的许多变体结合的热力学参数进行比较来测试和改进。由此产生的基于集成的观点不仅应该提供亲和性的结构和热力学起源，还应该允许访问特异性的决定因素。由于该模型旨在作为推导假设、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被编码到Mathematica笔记本中，这些笔记本可以根据要求分发给大学外UTMBand内配备适当设备的实验室。教育部分包括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。除了共同开发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展开，在这些课程中，学生（和教师）将学习各种将计算方法纳入自己研究的策略。非技术计算机技术的最新进步，加上生物数据库近乎指数级的增长，催生了生物信息学领域的迅速发展。在这个新兴领域内，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，在这项工作中就是这样，研究工作集中在整合结构（例如蛋白质数据库）和热力学数据库来推导分子识别、变构和信号转导的模型。在这个新的计算时代，生物学手头的任务不仅是发展方法本身，而且要提供一种媒介，通过这种媒介，这些方法可以在小组之间传播，并提供将这些方法纳入各种研究专业的策略。这项研究和教育结合的计划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（如mathematica），并为学生和教师提供方法和媒介方面的培训，来促进这些计算方法的使用。

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.