FRED TheoryΒΆ

FRED docks multiconformer molecules into a single receptor using an exhaustive search that systematically searches rotations and translations of each conformer of the ligand within the active site. Following the exhaustive search the top scoring poses are optimized and assigned a final score. These two steps are described in more detail below

Exhaustive Search

  1. Enumerates, to given resolution, every possible rotation and translation of each conformer of the ligand being docked within a box enclosing the active site. The resolution of the exhaustive search is determined by the overall resolution setting of -dock_resolution flag.
  2. Discard poses that either clash with the protein or extend too far from the binding site using the receptor’s negative image outer contour (see Negative Image section).
  3. If the negative image inner contour is enabled discard any poses that do not have at least one heavy atom that falls within the inner contour. (see Negative Image section).
  4. Discard any poses that do no match any user specified constraints. (see Constraints section).
  5. Score all remaining poses using Chemgauss3.
  6. Sort poses by score and pass the top scoring poses to optimization.

Optimization

  1. Enumerate nearby positions of each pose by having the initial pose take one positive and one negative step for each translational and rotational degree of freedom (729 poses total). The resolution of these steps is half that of the exhaustive search, and is determined by the setting of the -dock_resolution flag.
  2. Each pose is scored with Chemgauss4.
  3. The best scoring poses are retained. The number of poses retained is determined by the setting of the -num_poses parameter.
  4. The overall score of the molecule, used to rank the molecule against other molecules in the docking database, is set to the best scoring pose’s score.