Ligand refinement with combined force field and shape potential

COMP 186

Stanislaw Wlodek, stan@eyesopen.com, Geoffrey Skillman, skillman@eyesopen.com, and Anthony Nicholls. OpenEye Scientific Software, 3600 Cerrillos Road, Suite 1107, Santa Fe, NM 87507
A procedure for fitting a ligand into its electron density with the use of MMFF force field potential and a Gaussian shape component has been developed. It employs a series of adiabatic optimizations of gradually increasing shape potential. Starting from a ligand connection table, conformers are generated, rigidly oriented to the density's shape, and optimized to fit the electron density. The final structures are realistically strained and fit the crystallographic data very well. We demonstrate the application of this process to a variety of ligand-protein complexes from the pdb.