1146-1-m37bi-PosePredictionProtocol.txt

Name

PoPSS-Lite

Software

Omega 3.0.0.1
ROCS 3.2.2.2
Glide 6.1

System Preparation Parameters

A maximum of 2000 conformations per ligand were generated using macrocycle mode of Omega
RefTverskyCombo coefficient was used for evaluating shape similarity

System Preparation Method

Ligand conformations for shape similarity calculations were generated using macrocycle mode of Omega. A maximum number of 2000 conformations per ligand was generated. Receptors were prepared using protein preparation utility of Maestro.

Pose Prediction Parameters

None

Pose Prediction Method

This method places a ligand conformation with highest 3D shape similarity with known crystal structure ligand into protein binding site and then refines the pose by performing energy minimization. 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 Glide-SP refine only protocol. Protein structures for were selected based on ROCS shape similarity calculation and the structures with highly shape similar crystal ligand was used. In cases, where highest shape similarity receptor could not be used due to clashes with placed conformation receptor with next best shape similarity score was used.

Answer 1

Yes

Answer 2

Yes