Pose predictions of 18 benzimidazole complexes using MD
Schrodinger/2016-3, CCDC/5.4.0
Ligands were prepared at pH 7.4 +/- 0.0. The stereochemistries were given in the isosmiles strings and were therefore kept. Proteins were prepared in the following manner: bond orders were assigned, hydrogen atoms added, disulfide bonds were generated, and water orientations were sampled. The charge states were kept at pH 7.0. Missing loops and side chains were constructed. The given residue confirmations were kept, with no alternative residue conformations examined.
Schrodinger ligand preparation and protein preparation wizard
The pose predictions in this set were docked using a protocol to examine the ligand similarity to known structures, and docked using Schrödinger'ss Glide or CCDC Gold. The complexes were minimized using SD for 10 steps and ABNR until a convergence threshold of 1.0 kcal/mol was reached. These complexes were simulated in a Langevin heat bath and nonbond cutoffs were set to be 10.0 A.
The best ranked structure was submitted to 25 ns molecular dynamics simulations using Desmond GPU. The simulations were analyzed by examining the average structure at 5 ns increments, the best pose was selected and a short force field minimization was performed on the ligand to remove any bad orientations of portions of the ligand from the average structure simulations. Only 18 of the benzimidazole structures are submitted for examination.