Anchor and Grow

2.7.1. Anchor-and-Grow

   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.