Computation in BioInformatics

15Prospects of Covalent Approaches in Drug Discovery: An Overview

Balajee Ramachandran¹, Saravanan Muthupandian² and Jeyakanthan Jeyaraman¹*

¹Structural Biology and Bio-Computing Lab, Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, India

²Department of Microbiology and Immunology, Division of Biomedical Science, School of Medicine, College of Health Sciences, Mekelle University, Mekelle, Ethiopia

Abstract

The computational methods are extensively used in the drug discovery research. The molecular modeling approach is widely employed to understand the mechanism of protein-inhibitor complex to provide more insights in the drug discovery process. The covalent inhibitor provides the plausible mechanism with the protein target which leads to identify promising drug candidates with increased potency and safety when compared to the non-covalent inhibitors. The substantial amount of computational approaches has been developed to understand the covalent interactions between protein-inhibitor complex. Still, it requires effective algorithm to overcome the challenges in the drug discovery research. In this review, we emphasize on the following themes, namely, (i) covalent inhibitors against the biological targets, (ii) applications of physical chemistry concepts in the covalent drug design, (iii) importance of the covalent target, (iv) recent framework on covalent docking, (v) S_N2 reactions in the computational approaches, and (vi) other crucial aspects in the ...