Supervised redock
Smina Vinardo/AutoDock Vina/Pymol 2.2.0/OpenEye Omega
The intiail 3D models from the SMILES codes were generated with OpenEye's Omega. The intiail 3D models of the receptor is left untouched, thus water is preserved in docking.
FragFP-DataWarrior was used to find the most structrually similar ligand bound to BACE-1 pdb structure to the 154 test ligands. If the similarity Tanimoto score is greater(or equal to) 0.8, the corresponding receptor pdb file was used, otherwise, 4KE1.cif was used (a high resolution BACE-1 structure bound to a macrocyclic ligand). The intiail 3D models from the SMILES codes were generated with OpenEye's Omega.
Vina or Vinardo scoring function. Num_modes 5 #max number of poses to generate. autobox_add 2 or 4 #Amount of buffer space to add to auto-generated box, 4 as default. It was reduced to 2 when ligands are docked outsize the active site. autobox_ligand #A survey of BACE macrocyclic structures shows 4KE0-1R8 is a good starting ligand binding site.na
Docking runs were executed with the above specified parameters while default values
were applied for the rest of the variables. The top five poses (if there are five) from the smina docking are submitted with this protocol. When Vinardo scoring function did not yield reasonbale geometric models (based on whether the docked models overlay well on the existing macrocyclic ligands structures), default vina scoring function was applied.
Yes
Yes