Fitting small molecules to electron density is a challenging problem. Small molecules with few rotatable bonds are amenable to hand placement in density. Add a few rotatable bonds, however, and the problem becomes factorially more complicated. Furthermore, unlike protein modeling, many small molecules are relatively unique entities whose conformation cannot be predicted from previous homologies.
FLYNN uses a high-quality conformational analysis and a fast rigid overlay to position ligands in density in conjunction with a combined forcefield to further position these conformations while, at the same time, minimizing ligand strain. FLYNN can automatically locate ligand density and automatically fit fragment cocktails, or, failing that, FLYNN can use a supplied bounding box in which to place the ligands of interest.
Ligands are fit to density, however the placements are scored and ranked based on the real space correlation coefficient (RSCC) and optionally protein based docking scores: Piecewise-Linear-Potential (PLP) and Chemscore.
FLYNN reads common map formats such as CCP4, CNX/CNS (XPLOR) and MTZ as well as OpenEye’s grid formats and a plethora of small molecule, protein and connection table formats.