Docking covalent targets for drug discovery: stimulating the computer-aided drug design community of possible pitfalls and erroneous practices.

Autor: Oyedele AK; Computational Biology/Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.; Department of Chemistry, University of New Haven, West Haven, CT, USA., Ogunlana AT; Computational Biology/Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria., Boyenle ID; Computational Biology/Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria. idboyenle@student.lautech.edu.ng.; Department of Chemistry and Biochemsitry, University of Maryland, Maryland, USA. idboyenle@student.lautech.edu.ng.; College of Health Sciences, Crescent University, Abeokuta, Nigeria. idboyenle@student.lautech.edu.ng., Adeyemi AO; Department of Medical Laboratory Technology, Lagos State College of Health, Lagos, Nigeria., Rita TO; Department of Medical Laboratory Technology, Lagos State College of Health, Lagos, Nigeria., Adelusi TI; Computational Biology/Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria., Abdul-Hammed M; Department of Pure and Applied Chemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria., Elegbeleye OE; Computational Biology/Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria., Odunitan TT; Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
Jazyk: angličtina
Zdroj: Molecular diversity [Mol Divers] 2023 Aug; Vol. 27 (4), pp. 1879-1903. Date of Electronic Publication: 2022 Sep 04.
DOI: 10.1007/s11030-022-10523-4
Abstrakt: The continuous approval of covalent drugs in recent years for the treatment of diseases has led to an increased search for covalent agents by medicinal chemists and computational scientists worldwide. In the computational parlance, molecular docking which is a popular tool to investigate the interaction of a ligand and a protein target, does not account for the formation of covalent bond, and the increasing application of these conventional programs to covalent targets in early drug discovery practice is a matter of utmost concern. Thus, in this comprehensive review, we sought to educate the docking community about the realization of covalent docking and the existence of suitable programs to make their future virtual-screening events on covalent targets worthwhile and scientifically rational. More interestingly, we went beyond the classical description of the functionality of covalent-docking programs down to selecting the 'best' program to consult with during a virtual-screening campaign based on receptor class and covalent warhead chemistry. In addition, we made a highlight on how covalent docking could be achieved using random conventional docking software. And lastly, we raised an alert on the growing erroneous molecular docking practices with covalent targets. Our aim is to guide scientists in the rational docking pursuit when dealing with covalent targets, as this will reduce false-positive results and also increase the reliability of their work for translational research.
(© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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