monte carlo free energy perturbation
MCPro
OPLS force field
RESP charges, at HF6-31G* level.
Windows per transformation: 20
Assumed pH 7.4
Typical simulation time per window: 50 ns
Monte Carlo thermostat with time constant of 2 ps
(etc.)
The ligands were represented by the OPLS-AA force field and the TIP4P water model was used.
Metropolis Monte Carlo statistical mechanics (MC)
calculations were performed for a single solute in a periodic cube with 500 water molecules at
25 C and 1 atm in the isothermal-isobaric ensemble using MCPro.
Maestro/Omega/MGLTools/Autodock Vina Method 1
Maestro/Omega/MGLTools/AutoDock Vina
Assumed pH 7.4
Tautomers considered
Gasteiger charges
Maestro's prepwizard was used to add hydrogens using default parameters.
All the waters were retained while GAFF force field parameters were assigned to the protein and all
ligands. The binding site residues, which were considered to be residues 56, 65, 200 and 210, were energy minimized.
Ligand conformational libraries were generated using OMEGA. The most stable
conformation found for each ligand was then used as a starting point for docking.
Preparation for docking with Vina was done using MGLTools where the ligand PDB files from
OMEGA were converted to PDBQTs by assigning charges and atom types. The binding site residues
above were treated as flexible and the grid box determined.
Iterated Local Search global optimizer search method
Exhaustiveness=50 #exhaustiveness of global search (default=8)
Vina scoring funtion (empirical + knowledge-based function)
Num_modes=5 #max number of poses to generate
Energy_range=5 #energy difference (kcal/mol) between the best and worst binding mode
Docking runs were executed with the above specified parameters while default values
were applied for the rest of the variables. The top 5 poses from the Vina docking are submitted with this protocol.