Pose prediction using FlexX
Leadit 2.3.2/Chem 3D 2016#
Assumed pH 7.4
Some structural Water molecules considered
Protonation of the active site residues
Leadit receptor preparation was used to add hydrogens using default parameters.
All the waters within the binding site were considered displaceable. The binding site residues, which were considered to be residues within 10 Angstrom distance from co-crystalized ligand.
Ligand conformational were generated And minimized using Chem3D 2016.
The binding site residues above were treated as rigid.
kept as default
The crystal structure of BACE for docking was selected using similarity search of the 20 proposed ligands In PubChem and then if the similar compounds had a co-crystallized structure with BACE the PDB structure was considered for docking. Five PDB structures were selected for subsequent validation steps. A hierarchical clustering strategy was employed to find the most similar co-crystalized ligand to the data set. In this step, structure features of the PDB structure such as resolution and R-free value were taken into account. At the end, structure 3CIB was selected for the docking study.All of the protein and ligand preparations have been carried out using leadit environment docking was performed using FlexX docking engine. First the protein structure retrieved form the PDB web site. Chain A selected for the study and a sphere with around 10 Angstrom diameter was considered as the binding pocket. A preliminary self-docking approved the accuracy of the software to re-produce the binding pose of the co-crystallized ligand. The 3D ligand structures were given to the Leadit. The 3D structures were minimized using Chem3D. The Leadit is applying an innovative method on the binding site residues to predict the best ionization state and direction of the hydrogens. After these hydrogen bond network optimization the several water molecules were considered as displaceable during the dockings runs. The results clustered automatically and the five best proposed solutions for each ligand were submitted.
No
Pose prediction using FlexX
Leadit 2.3.2/Chem 3D 2016
Assumed pH 7.4
Leadit receptor preparation was used to add hydrogens using default parameters.
All the waters within the binding site were considered displaceable. The binding site residues, which were considered to be residues within 10 Angstrom distance from co-crystalized ligand. Ligand conformational were generated And minimized using Chem3D 2016.The binding site residues above were treated as rigid.The crystal structure of BACE for docking was selected using similarity search of the 20 proposed ligands In PubChem and then if the similar compounds had a co-crystallized structure with BACE the PDB structure was considered for docking. Five PDB structures were selected for subsequent validation steps. A hierarchical clustering strategy was employed to find the most similar co-crystalized ligand to the data set. In this step, structure features of the PDB structure such as resolution and R-free value were taken into account. At the end, structure 3CIB was selected for the docking study.All of the protein and ligand preparations have been carried out using leadit environment docking was performed using FlexX docking engine. First the protein structure retrieved form the PDB web site. Chain A selected for the study and a sphere with around 10 Angstrom diameter was considered as the binding pocket. A preliminary self-docking approved the accuracy of the software to re-produce the binding pose of the co-crystallized ligand. The 3D ligand structures were given to the Leadit. The 3D structures were minimized using Chem3D. The Leadit is applying an innovative method on the binding site residues to predict the best ionization state and direction of the hydrogens. After these hydrogen bond network optimization the several water molecules were considered as displaceable during the dockings runs. The results clustered automatically and the enrgy for the best proposed solution for each ligand was submitted.
No