Semi-Flexible Docking (Flexible-rigid docking) Semi-flexible docking (Figure ) is a computational method that combines the features of rigid and completely flexible docking approaches. It aims to balance computational efficiency with the ability to account for ligand flexibility during the docking process. Numerous molecular docking programmes, such as DiffBind ( ) and CANDOCK ( ), have been documented in the literature and can be utilised to explore ligand-receptor interactions. Semi-flexible docking, such as DiffBind ( ), involves keeping the receptor structure fixed while allowing the ligand to undergo limited conformational flexibility. This flexibility enables the ligand to make structural alterations to match the binding site better. The semi-flexible docking approach recognises the significance of considering the flexibility of ligands in accurately forecasting binding modes and affinities, especially in situations where ligands can take on many conformations when binding to the receptor ( ). Semi-flexible docking methods utilise algorithms and scoring functions that can effectively explore the flexibility of ligands while quickly sampling the space for binding. Semi-flexible docking is vital to enhance the reliability of virtual screening and drug design studies by effectively modelling ligand-receptor interactions while considering computing cost and accuracy ( ).