High strain energies of bound ligands: What is going on?

CINF 76

Paul Labute, paul@chemcomp.com, Chemical Computing Group, Inc, 1010 Sherbrooke Street W, Suite 910, Montreal, QC H3A 2R7, Canada
The prediction of the bioactive bound conformation of a candidate ligand is important for computational methodologies such as pharmacophore search and docking. The strain energy of a conformation (relative to theglobal minimum energy) is often used as a criterion for rejection of a conformation from consideration. Recent molecular mechanics studies using ligand-receptor complexes from the PDB have suggested that high strain energies (> 10 kcal/mol) are not only possible but routinely observed. We present the results of computational experiments that attempt to explain these observations and determine their validity.