Next Article in Journal
Development and Validation of 697 Novel Polymorphic Genomic and EST-SSR Markers in the American Cranberry (Vaccinium macrocarpon Ait.)
Next Article in Special Issue
Reduction of False Positives in Structure-Based Virtual Screening When Receptor Plasticity Is Considered
Previous Article in Journal
Synthesis and Biological Evaluation of Novel 6-Hydroxy-benzo[d][1,3]oxathiol-2-one Schiff Bases as Potential Anticancer Agents
Article Menu

Export Article

Open AccessReview
Molecules 2015, 20(2), 1984-2000; doi:10.3390/molecules20021984

Theory and Applications of Covalent Docking in Drug Discovery: Merits and Pitfalls

Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, South Africa
*
Author to whom correspondence should be addressed.
Academic Editor: Rino Ragno
Received: 12 November 2014 / Revised: 19 December 2014 / Accepted: 12 January 2015 / Published: 27 January 2015
(This article belongs to the Special Issue Molecular Docking in Drug Design)
View Full-Text   |   Download PDF [1935 KB, uploaded 27 January 2015]   |  

Abstract

he present art of drug discovery and design of new drugs is based on suicidal irreversible inhibitors. Covalent inhibition is the strategy that is used to achieve irreversible inhibition. Irreversible inhibitors interact with their targets in a time-dependent fashion, and the reaction proceeds to completion rather than to equilibrium. Covalent inhibitors possessed some significant advantages over non-covalent inhibitors such as covalent warheads can target rare, non-conserved residue of a particular target protein and thus led to development of highly selective inhibitors, covalent inhibitors can be effective in targeting proteins with shallow binding cleavage which will led to development of novel inhibitors with increased potency than non-covalent inhibitors. Several computational approaches have been developed to simulate covalent interactions; however, this is still a challenging area to explore. Covalent molecular docking has been recently implemented in the computer-aided drug design workflows to describe covalent interactions between inhibitors and biological targets. In this review we highlight: (i) covalent interactions in biomolecular systems; (ii) the mathematical framework of covalent molecular docking; (iii) implementation of covalent docking protocol in drug design workflows; (iv) applications covalent docking: case studies and (v) shortcomings and future perspectives of covalent docking. To the best of our knowledge; this review is the first account that highlights different aspects of covalent docking with its merits and pitfalls. We believe that the method and applications highlighted in this study will help future efforts towards the design of irreversible inhibitors. View Full-Text
Keywords: covalent docking; covalent inhibition; covalent interactions; irreversible inhibition covalent docking; covalent inhibition; covalent interactions; irreversible inhibition
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Kumalo, H.M.; Bhakat, S.; Soliman, M.E.S. Theory and Applications of Covalent Docking in Drug Discovery: Merits and Pitfalls. Molecules 2015, 20, 1984-2000.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top