Ligand Preparation

Ligand preparation converts the two-dimensional chemical structure of each candidate compound into an energetically reasonable, correctly protonated, and...

Ligand preparation converts the two-dimensional chemical structure of each candidate compound into an energetically reasonable, correctly protonated, and stereochemically defined three-dimensional model suitable for docking. This process generates appropriate tautomeric and protonation states at physiological pH, enumerates stereoisomers where stereochemistry is not explicitly defined in the input structure, assigns partial atomic charges required by the docking scoring function, and performs an initial energy minimisation to remove unfavourable internal steric strain, ensuring that each ligand entering the docking calculation represents a chemically realistic starting conformation rather than an arbitrary two-dimensional projection.