Covalent Docking is a computational technique used to predict the binding mode of covalent ligands to their target proteins. Unlike traditional docking methods that only model non-covalent interactions, covalent docking also simulates the formation of a covalent bond between a reactive species in a ligand and a reactive species in a residue on the protein. This is particularly important for molecules designed to probe irreversible or reversible covalent binding mechanisms that can lead to enhanced potency and selectivity.
Importance in Computational Drug Discovery
- Enhanced Potency: Covalent inhibitors often exhibit higher potency due to them inherently having much slower off-rates or increased residence times.
- Improved Selectivity: By targeting specific residues that can form covalent bonds, these ligands can achieve greater selectivity, reducing off-target effects.
- Overcoming Resistance: Covalent inhibitors can be effective against targets with mutations that confer resistance to non-covalent inhibitors.
- Longer Duration of Action: The irreversible binding can result in a prolonged duration of action, which can be beneficial in some therapeutic settings.
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