ovz75-LigandScoringProtocol.txt

Name

Vina Score

Software

Vina Score

Parameters

default

Method

Vina Score, using default parameters

Answer 1

No

ovz75-PosePredictionProtocol.txt

Name

A template-based method, XDZ_1

Software

OMEGA 2.5/SHAFTS/AMBER11/ITScore2

System Preparation Parameters

maxconfs=500 #OMEGA

System Preparation Method

All the released crystal structures of human
JAK2 protein-small molecule complexes were collected from the Protein Data Bank.
Ligand conformational libraries were generated using OMEGA.

Pose Prediction Parameters

AM1-bcc #atomic charges for ligands
AMBER03 force field
Generalized Amber force field (GAFF)
Re-scoring function, ITScore2 #ITScore version 2.0

Pose Prediction Method

For a query compound, up to 500 ligand conformations were generated
using OMEGA. Each ligand conformer was superimposed on co-bound ligand in known
JAK2-small molecules complexes using SHAFTS. Then, complexes formed by the superimposed query ligand and
proteins were ranked by ranked using an in-house knowledge-based scoring function ITScore2.
Then, the top selected protein-query compound complexes was used as the initial structure for the next
MD refinement with AMBER11. Atomic partial charges of each ligand were assigned using
Antechamber based on the AM1-bcc method after ligand minimization. Using the Leap module,
the AMBER03 force field and the Generalized Amber force field (GAFF) were applied to the
receptor and to the ligand, respectively. The hydrogen atoms, water molecules and counter
ions were also added to the complexes. The solvated complexes were then minimized in two steps.
During the first step, the solvent molecules were minimized for 1000 steps via steepest descent,
followed by 3000 steps via conjugate gradient. A 500 kcal/mol/Å^2 restraint was imposed on all
the protein atoms and ligand atoms. During the second step, the protein-ligand complexes and the
solvent were both minimized for 10,000 steps via the steepest descent method, followed by conjugate
gradient minimization until the energy gradient of the system converged to 0.01 kcal/mol/Å.

Answer 1

No

Answer 2

Yes