Rapid Computational Analysis of Biomolecular Properties

该奖项将支持开发新的算法，用于快速分析大分子构象，并将其集成到表面属性的图形表示和分析(GRAPH)计算机程序中。GRAPH被设计为一种研究工具，以促进蛋白质和核酸的结构和能量性质的分析。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。这进而使用快速表面绘制算法来表示，以供图形工作站显示和操作。这个项目的基本科学部分是基于通过使用溶剂的连续处理来计算大分子的构象和结合自由能的能力。GRASH将开发新版本的Delphi静电学程序和一种新的疏水效应处理方法，该方法基于表面积和曲率来评估相关的相互作用。当与传统的“气相”力场相结合时，这些方法应该允许完整地评估自由能，包括溶剂效应。我们计划开发算法，使其能够在相对较短的时间内进行准确的计算。通过将它们完全整合到GRAP中，我们打算将这些方法提供给科学界。GRASH的图形组件强调将所有物理属性映射到分子表面。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。它将在图形工作站上运行，这意味着它的功能将随时提供给生物和化学界的大量研究人员。

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.