Autodock Vina scoring based on conformations from flexible CDOCKER.
Autodock Vina
Assuming pH 7 to assign the ligand's protanation state.
For each ligand, multiple conformations of protein-ligand complex were found
using flexible CDOCKER. These conformations were scored using Autodock Vina. The final
score for the ligand was calucated using the average of these Vina scores.
Flexible CDOCKER (CHARMM DOCKER)
Flexible CDOCKER
CHARMM36 force field for proteins and CHARMM General Force Field (CGenff 3.0.1) for ligands. Assuming pH 7 to assign the ligand's protanation state.
The force field for the ligands was generated using the program MATCH based on CGenff force field.
In simulated annealing, the temperature is first increased from 300K to 1000K in 6000 steps with a step size of 1.5fs. Then the temperature is decreased from 1000K to 50K in 14000 steps with the same step size. van de Waals energy switch function and electrostatic switch function are used from 12 to 14 angstrom. A distance dependent dielectric constant is used with epsilon of 3.
1. Inital pose preparation.
For the ligands with ID of 1 to 36, the crystal structures of protein-ligand complex are used as the starting conformations. For the other ligands, the starting conformation is obtained by docking the ligand ontfo the crystal structure of proteins which bind with similar ligands out of the first 36 ligands.
2. Flexible CDOCKER.
The starting conformation of the protein-ligand complex is first minimized. Then 10 runs of simulated annealing is used to search for the lowe energy conformations. During the simulate annealing, the protein side chains which have heavy atoms within 5 angstrom of the ligand is flexible and all other parts of protein is fixed. The end conformations from simulated annealing are used for scoring.