Integrated Covalent Drug Design Workflow Using Site Identification by Ligand Competitive Saturation.

ABSTRACT: Covalent drug design is an important component in drug discovery. Traditional drugs interact with their target in a reversible equilibrium, while irreversible covalent drugs increase the drug-target interaction duration by forming a covalent bond with targeted residues and thus may offer a more effective therapeutic approach. To facilitate the design of this class of ligands, computational methods can be used to help identify reactive nucleophilic residues, frequently cysteines, on a target protein for covalent binding, to test various warhead groups for their potential reactivities, and to predict noncovalent contributions to binding that can facilitate drug-target interactions that are important for binding specificity. To further aid covalent drug design, we extended a functional group

SUBMITTER: Yu W 

PROVIDER: S-EPMC10205696 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature