Anchor and Grow

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The process of docking a molecule using the anchor-first strategy is shown in the Workflow for Anchor-and-Grow Algorithm. First, the largest rigid substructure of the ligand (anchor) is identified (see Identification of Rigid Segments) and rigidly oriented in the active site (orientation) by matching its heavy atoms centers to the receptor sphere centers (see Orienting the Ligand). The anchor orientations are evaluated and optimized using the scoring function (see Scoring) and the energy minimizer (see Minimization). The orientations are then ranked according to their score, spatially clustered by heavy atom root mean squared deviation (RMSD), and pruned (see Pruning the Conformation Search Tree). Next, the remaining flexible portion of the ligand (see Identification of Flexible Layers) is built onto the best anchor orientations within the context of the receptor (grow). It is assumed that the shape of the binding site will help restrict the sampling of ligand conformations to those that are most relevant for the receptor geometry. The conformation of a flexible molecule may be searched or relaxed using the flexible_ligand option. Only the torsion angles are modified, not the bond lengths or angles. Therefore, the input geometry of the molecule needs to be of good quality. A structure generated by ZINC is sufficient. The torsion angle positions reside in an editable file (see flex_drive.tbl on page 111) which is identified with the flex_drive_file parameter. Internal clashes are detected during the torsion drive search based on the clash_overlap or internal_energy parameters, which are independent of scoring function.