GrAMBina
GrAMBina, AMBER, Gromacs, Chimera, RDKIT
Assumed pH 6.0
GAFF charges
Homology models (Using Modeller) of BACE receptors containing macrocycles were generated to remove all missing ressidues. The structures with the ligand bound to the receptors were minimized using Gromacs 2018 and the latest AMBER forcefield. System Preparation Method: These receptors were used in an ensemble docking protocol. System Preparation Method: Ligands were generated using RDKIT (max 10-conformers). System Preparation Method: In order to generate binding poses for ligands, the macrocycle was broken and the connecting atoms were replaced with "Glue" atoms. System Preparation Method: xs-optimized radii of atoms (based on the Gromacs/AMBER minimized poses) in the receptor, ligand and GrAMBina package (a modified smina version) were used for pose prediction. System Preparation Method: A strong gaussian potential was added so that these Glue atoms are next to each other in the final pose with a length of 1.51 A apart. System Preparation Method: Best poses were visually selected.
Iterated Local Search global optimizer search method
Exhaustiveness=24 #exhaustiveness of global search (default=8)
GrAMBina scoring funtion (empirical + knowledge-based function)
Num_modes=1 #max number of poses to generate
Energy_range=5 #energy difference (kcal/mol) between the best and worst binding mode
After docking best poses were visually selected.
Yes
No