STRUCTURE FUNCTION RELATIONSHIPS BY SENSITIVITY ANALYSIS

计算建模正在成为一种普遍的工具， 生物结构与功能的关系，最近， 生物活性分子的发展。 生物分子建模将清楚地 发挥着越来越重要的作用，因为它提供了一个系统的手段， 通过对高层次的复杂性进行分类， 生物分子系统 尽管令人兴奋和日益增长的 生物分子建模的成功，一些严重的问题， 出现了关于可靠性和充分利用的问题， 技术. 在预测可靠性的情况下， 建模结果显然又取决于输入的质量 潜在的使用功能。 第二，这将是非常有价值的， 生成结构-功能关系的定量测量 特别是用于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 改进势函数在分子力学和分子动力学中应用 模拟，并阐明生物分子的结构-功能关系 通过建立结构-势能关系。 具体 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 观察和潜力。 工作的一个关键要素是确定关键 势的特征，这是真正重要的决定， 生物分子的特殊结构或功能。 方法来研究 结构-结构相关性和结构弛豫途径将 也要发展。 敏感性分析所需的软件 研究将被写入和测试，通过应用它们来学习简单的 肽，蛋白质牛胰蛋白酶抑制剂（BPTI），胰蛋白酶 和胰蛋白酶原，以及从蛋白质数据库中选择的蛋白质。 而 测试软件，对蛋白质的原理有用的见解 构象，和生物分子功能的决定因素也将是 获得。

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.