PoPSS
Omega 3.0.0.1
ROCS 3.2.2.2
Rosetta Suite 2015.25
A maximum of 2000 conformations per ligand were generated using macrocycle mode of Omega
RefTverskyCombo coefficient was used for evaluating shape similarity
Ligand conformations for shape similarity calculations were generated using macrocycle mode of Omega. A maximum number of 2000 conformations per ligand was generated. Receptors for docking were prepared using fast_relax protocol of Rosetta.
None
Our method PoPSS amalgamates ligand 3D shape similarity with RosettaLigand "high resolution" docking. PoPSS place a ligand conformation with highest 3D shape similarity with known crystal structure ligand into protein binding site and then refines the pose by repacking the side chain and performing energy minimization with a Monte Carlo algorithm. Ligand conformations were generated using Omega program. All available ligand bound crystal structures of BACE-1 from PDB were downloaded and were superimposed onto BACE-1 crystal structure (PDB code 5YGX). Relevant ligands were extracted and ligand 3d shape similarity calculations between ligand conformations and crystal structure ligand were performed. Shape similarity calculations were performed using ROCS. Top scoring ligand conformation for each ligand was placed into target protein binding site and refined using sidechain repacking and Monte Carlo energy minimization. Sidechain repacking and Monte Carlo energy minimization was performed using RosettaScripts. Protein structures for docking were selected based on ROCS shape similarity calculation and the structures with highly shape similar crystal ligand were used. Two hundred poses were generated that were sorted using "interface delta" score. Pose with best "interface delta" score was selected as final pose.
Yes
Yes