PROFEC (Pictorial Representation Of Free Energy Changes) is a set of software tools for carrying out and displaying extrapolative free energy calculations. Specifically, the PROFEC software suite calculates the free energy for inserting a specified test particle at a grid of points near the ligand of interest. A weighted electrostatic potential is also calculated for each position on this grid. These two (van der Waals and electrostatic) grids can be visualized and overlaid on a three-dimensional structure of the ligand or ligand-receptor complex to suggest positions where modifications to the ligand would improve binding. The main strengths of PROFEC are its unbiased evaluation of possible modifications and the ability to explicitly include the effect of solvation in the analysis. The main weakness is its inability to deal with modifications at multiple sites or modifications that induce large confomational changes.
PROFEC consists of three programs: makeGrid and makeDiffGrid generate and manipulate the "free energy" grids, while the Field program allows interactive visualization and manipulation of the grid data. A detailed description of the PROFEC algorithms and a demonstration of its application to the benzamidine-trypsin complex can be found in R.J. Radmer and P.A. Kollman, "The application of approimate free energy calculation methods to structure based ligand design: Tyrpsin and its complex with inhibitors" (1997) J. Comput.-Aided Mol. Des. in press.