The serendipitous discovery of covalent inhibitors and their characteristic potency of inducing
irreversible and complete inhibition in therapeutic targets have caused a paradigm shift from the use of
non-covalent drugs in disease treatment. This has caused a significant evolution in the field of covalent
targeting to understand their inhibitory mechanisms and facilitate the systemic design of novel covalent
modifiers for ‘undruggable’ targets. Computational techniques have evolved over the years and have
significantly contributed to the process of drug discovery by mirroring the pattern of biological occurrences
thereby providing insights into the dynamics and conformational transitions associated with biomolecular
interactions. Moreover, our previous contributions towards the systematic design of selective
covalent modifiers have revealed the various setbacks associated with the use of these conventional
techniques in the study of covalent systems, hence there is a need for distinct approaches. In this review,
we highlight the modifications and development of computational techniques suitable for covalent systems,
their lapses, shortcomings and recent advancements.
Keywords: Covalent, Irreversible, Inhibition, Computational techniques, Molecular dynamics, Covalent docking, QM/MM.
Rights & PermissionsPrintExport