Do Glide docked poses depend on the initial ligand conformations?
Some variation in the poses and GlideScores is expected when starting from different input conformations of a particular ligand. This is particularly true when the bond lengths and angles changes, but is also true for input conformations with only torsional differences. Sampling, docking, and scoring in a timely manner is a challenging problem. Dependence on the input conformation arises because of the complicated grid-based potentials and difficulties in thoroughly sampling the docked poses. In addition, Glide generates new ligand conformations through torsional variations only, so any differences in bond lengths and angles in the input ligand structures will persist through the docked poses, resulting in scoring and pose differences. In general, ligands that are good binders will fluctuate less than poor binders. A poor binder or inactive is less likely to have a low energy solution that can be found independent of small variations. Also, poor binders are more likely to encounter the
