Table 3a.

Docking studies that included side-chain flexibility through rotamer libraries. Caveats for each method are similar in that flexibility of the side chains alone has limited success in describing receptor motion for most binding events and the implementation of a rotamer library limits the conformational space that can be sampled

Method	Target	Flexibility	Results	Author
Rotamer Library	Trypsin, McPC 603	Rotameric states sampled for all side chains within 10 Å of binding site	Limited by the lack of a solvation term RMSD of closest structure to the bound pose from the crystal was 0.7 Å for trypsin, 0.8 Å for McPC 603; in neither case was the closest pose also the lowest energy structure Did not recover a good correlation between binding energy and RMSD to crystal structure	Leach (1994)
SOFTSPOTS/PLASTIC	Thymidylate synthase	Identified variation based on structural comparison (or binding site analysis) Disregarded polar residues Retained hydrophobic residues and loops for potential adaptation Subjected 3 residues to rotamer variation Minimized docked pose	Minimized, remodeled complex achieved reasonable energy scores for two potent inhibitors Found −51.5 kcal/mol for ligand BW1843U89 and −49.7 kcal/mol for CB3717 for cross-docking with side-chain flexibility Found −32.8 kcal/mol for CB3717 and −44.7 kcal/mol for BW1843U89 with rigid docking Scores from native docking were −56.5 kcal/mol for BW1843U89 and −52.9 kcal/mol for CB3717	Anderson et al. (2001)