47kuq-LigandScoringProtocol.txt

Name

Thermal MM-GBSA

Software

Desmond molecular dynamics simulation and Prime molecular mechanics applications in Schrodinger 2017-4 suites.

Parameters

OPLS2005 forcefield

Method

Multiple snapshots were generated using molecular dynamics simulation and the snapshots were used for calculating binding free energies of ligands.

Answer 1

No

47kuq-PosePredictionProtocol.txt

Name

Survival of the Fittest algorithm (as implemented in QM-Polarized Ligand Docking of Schrodinger, ref: Cho, A. E.; Guallar, V.; Berne, B.; Friesner, R. A., J. Comput. Chem., 2005, 26, 915-931)

Software

QM-Polarized Ligand Docking (Glide 6.6, QSite 6.6 and Maestro 10.1 - Schrodinger suites)

System Preparation Parameters

OPLS2005 force field

System Preparation Method

The crystal stucture of ABL1 was downloaded from RCSB protein data bank and the the structure was treated with the Protein Preparation Wizard module of the Schroodinger suite for docking.
The module assigns correct bond orders and adds hydrogens based on Epik calculations for appropriate pKa values.
Protein Assignment utility of the module resolved the structural ambiguities of the crystal structure.
Restrained minimization was performed to relax only the added hydrogens using Impact with OPLS2005 force field.
Mutated structures of ABL1 were generated manually and the mutated residues were structually optimized by Prime structure optimization.

Pose Prediction Parameters

OPLS2005 force field for molecular mechanics calculation, DFT calculation B3LYP functional and 6-31G** basis set,

Pose Prediction Method

The QM-Polarized Ligand Docking (QPLD) begins with a Glide docking job that generates several geometrically unique protein-ligand complexes. QSite, a QM/MM program, is then performed for a single-point energy calculation on each complex, treating the ligand only as QM region with DFT calculation and deriving ESP charges using electrostatic potential fitting. Subsequently, Glide is used to re-dock the ligand using each of the ligand charge sets calculated in the previous step, and the QPLD finally returns the most energetically favorable pose by Coulomb-van der Waals energy.

Answer 1

No

Answer 2

No