Rapid Computational Analysis of Biomolecular Properties

该合同将支持开发用于快速分析大分子构象的新算法，并将其集成到表面性质图形表示和分析（GRASP）计算机程序中。GRASP是一种研究工具，用于分析蛋白质和核酸的结构和能量特性。该程序与现有程序的不同之处在于，它允许完全基于可以映射到分子表面的物理性质来快速评估构象和结合能。这反过来又使用快速表面渲染算法表示，供图形工作站显示和操作。本项目的基础科学组成部分是基于通过使用溶剂连续处理来计算大分子的构象和结合自由能的能力。GRASP将利用新版本的DelPhi静电程序和疏水效应的新处理方法，该程序基于表面积和曲率评估相关的相互作用。当与传统的“气相”力场相结合时，这些方法应该允许包括溶剂效应在内的自由能的完整评估。我们计划开发算法，使在相对较短的时间内进行精确的计算成为可能。通过将它们完全整合到GRASP中，我们打算将这些方法提供给科学界。GRASP的图形组件强调将所有物理性质映射到分子表面。这种能力使研究人员有可能获得对蛋白质和核酸结构和设计的新见解。事实上，它将在图形工作站上运行，这意味着它的功能将随时可供生物和化学领域的大量研究人员使用。

This award will support the development of new algorithms for the rapid analysis of macromolecular conformation and for their integration into the Graphical Representation and Analysis of Surface Properties (GRASP) computer program. GRASP was designed as a research tool to facilitate the analysis of the structural and energetic properties of proteins and nucleic acids. The program is distinct from existing ones in that it allows rapid evaluation of conformational and binding energies based entirely on physical properties that can be mapped onto the molecular surface. This in turn is represented using a fast surface rendering algorithm, for display and manipulation by graphics workstations. The underlying scientific component of this project is based on the ability to calculate the conformational and biding free energies of macromolecules by using a continuum treatment of solvent. GRASP will exploit a new version of the DelPhi program for electrostatics and a new treatment of the hydrophobic effect which evaluates the relevant interactions based on surface area and curvature. When combined with a traditional "gas phase" force field, these methods should allow a complete evaluation of free energies including solvent effects. We plan to develop algorithms which make it possible to carry out accurate calculations in relatively short periods of time. By fully integrating them into GRASP we intend to make these methods available to the scientific community. The graphical component of GRASP emphasizes the mapping of all physical properties onto the molecular surface. This ability gives researchers the potential to obtain novel insights into protein and nucleic acid structure and design. The fact that it will run on graphics workstations implies that its capabilities will be readily available to a large number of researchers in the biological and chemical communities.