Each identified partial conformation of the docked seed fragments is gradually grown into the original ligand by addition of non-seed fragments using the A* search algorithm. This can be done at different levels of protein flexibility. Protein minimization may be performed at each step of the linking process or only at the end when the compound has been reconstructed. Each seed fragment is linked to adjoining fragments according to the connectivity of the original compound. Each added non-seed fragment is rotated 360° about the bond vector at 60° increments. If the user has specified full protein flexibility, the resulting conformation of the partial compound and the protein is subjected to knowledge-based energy minimization using the RMC15 scoring function as for intermolecular forces. Simultaneously, bonds, angles and torsions of the partial compound and the protein are minimized using the standard AMBER molecular mechanics energy minimization. This procedure uses the popular OpenMM software package, specifically its implementation of the L-BFGS minimization algorithm . With each round of minimization, the RMR6 score is calculated for the protein-compound interactions, and the scored conformation is added to the priority queue which consists of the growing compound conformations in the order from the best-scored to the worst-scored.