Why does Glide produce poses with close intra-ligand contacts?
Close intramolecular contacts can occur in docked poses because Glide uses a truncated version of the OPLS-AA force field for the ligand that does not calculate intra-ligand interactions beyond 1,4 pairs. We deliberately allow these close contacts as a way of compensating for the lack of receptor flexibility. While these close contacts may seem unphysical, the scoring/ranking is more accurate this way (compared to rejecting such poses). In real systems, the shape of the binding pocket would adjust to accommodate more relaxed ligand conformations. To explore the binding modes more closely for select poses, you may want to employ a post-docking process such as Prime MM-GBSA, MacroModel eMBrAcE, Liaison , or Induced Fit Docking . With these flexible-receptor tools, the close contacts can be removed, and more realistic ligand conformations and binding modes can be obtained. An alternative for HTVS and SP docking is to use post-docking minimization, which was introduced in Glide 4.5, to imp
