STRUCTURE FUNCTION RELATIONSHIPS BY SENSITIVITY ANALYSIS

计算建模正在成为一种普遍的工具，用于理解 生物结构-功能关系以及最近指导 生物活性分子的发展。生物分子模拟将清楚地 发挥着越来越重要的作用，因为它为 对中固有的高度复杂性进行排序 生物分子系统。尽管令人兴奋和不断增加 在生物分子模拟方面的成功，一些严肃的问题和 出现了关于可靠性和充分开发的问题 技巧。在预测可靠性的情况下， 建模结果显然取决于输入的质量 所采用的势函数。其次，这将是非常有价值的 生成结构-功能关系的量化度量 尤其是生物活性分子的设计。 这项研究的长期目标是开发方法来帮助测试和 改进势在分子力学和分子动力学中的应用 模拟，并阐明生物分子结构-功能关系 通过建立结构-势能关系。具体的 该项目的目的是开发系统灵敏度的方法。 分析研究结构或热力学之间的关系 可观测性和势能。这项工作的一个关键要素是确定关键 势能的特征对确定 生物分子的特殊结构或功能。研究方法 结构-结构关联和结构松弛路径将 也被开发出来。敏感性分析所需的软件 研究将通过应用它们来编写和测试简单学习 多肽，蛋白质牛胰腺胰蛋白酶抑制物(BPTI)，胰酶 和胰酶原，并从蛋白质数据库中选择蛋白质。而当 测试软件，对蛋白质的原理有帮助的见解 构象，生物分子功能的决定因素也将是 收获了。

Computational modelling is becoming a pervasive tool both for understanding biostructure-function relationships and most recently to guide the development of bioactive molecules. Biomolecular modelling will clearly play an increasingly important role as it provides a systematic means for sorting through the high levels of complexity inherently present in biomolecular systems. Notwithstanding the exciting and increasing successes with biomolecular modelling, a number of serious questions and issues arise concerning the reliability and full exploitation of the techniques. In the case of predictive reliability, the quality of the modelling results clearly depends in turn on the quality of the input potential functions employed. Secondly, it would be very valuable to generate quantitative measures of structure-function relationships especially for the design of bioactive molecules. The long-term goal of this research is to develop methods to help test and improve potentials used in molecular mechanics and molecular dynamics simulations, and to elucidate biomolecular structure-function relationships through the establishment of structure-potential relations. The specific aim of this project is to develop methods of systematic sensitivity analysis to study the relationships between structural or thermodynamic observables and potentials. A key element of the work is to identify key features of a potential that are truly significant in determining a particular structure or function of a biomolecule. Methods to study structure-structure correlations and structural relaxation pathways will also be developed. The necessary software for the sensitivity analysis studies will be written and tested by applying them to study simple peptides, the protein bovine pancreatic trypsin inhibitor (BPTI), trypsin and trypsinogen, and selected proteins from the Protein Data Bank. While testing the software, useful insights into the principles of protein conformation, and the determinants of biomolecular functions will also be gained.