QMMM/PBSA (Quantum mechanics/Molecular mechancis - PoissonBoltzmann Surface Area)
QSite 6.6
DFT calculation (B3LYP/6-31G**), OPLS2005 force field, PoissonBoltzmann solvation model
The binding energy is calculated by: Ebind = E(complex) - E(receptor) - E(ligand), For the calculation of E(complex), only ligand molecule was treated as QM region and the other region is treated as MM region under PBSA solvation model. Energies of ligand and receptor molecules were calculated seperately.
Yes
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)
QM-Polarized Ligand Docking (Glide 6.6, QSite 6.6 and Maestro 10.1 - Schrodinger suites)
OPLS2005 force field
The crystal stucture of Cathepsin S 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.
OPLS2005 force field for molecular mechanics calculation, DFT calculation B3LYP functional and 6-31G** basis set,
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.
Yes
Yes