Rapid Computational Analysis of Biomolecular Properties

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.