Theoretical Insight into the Library Screening Approach for Binding of Intermolecular G-Quadruplex RNA and Small Molecules through Docking and Molecular Dynamics Simulation Studies

Roy, S and Ali, A and Bhattacharya, S (2021) Theoretical Insight into the Library Screening Approach for Binding of Intermolecular G-Quadruplex RNA and Small Molecules through Docking and Molecular Dynamics Simulation Studies. In: Journal of Physical Chemistry B, 125 (21). pp. 5489-5501.

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Abstract

The interactions of intermolecular G-quadruplex RNA and small molecules have been investigated by computational studies. Various anthraquinone, bisbenzimidazole, and carbazole-benzimidazole based ligands have shown a distinct preference to G-quadruplex structures as opposed to the corresponding duplex forms of DNA that were docked with telomeric G-quadruplex RNA. The comparative binding study of such ligands with G-quadruplex (G4) RNA showed higher binding affinities toward carbazole-benzimidazole ligands than those of the anthraquinone and bisbenzimidazole based ligands. A molecular dynamics simulation study was used to examine quadruplex-ligand interactions. Analysis of the binding free energy indicated the formation of the thermodynamically favorable RNA-ligand complex. The formation of several H-bonding interactions and the change of the solvent accessible surface area (SASA) also support the effective binding of the carbazole-benzimidazole ligands with G4 RNA structures. Thus, the library screening approach has assisted in getting a structure-activity relationship for the selected small molecules toward the G-quadruplex RNA binding, which can be applied in the targeting of G-quadruplex RNA medicated anticancer therapeutics. © 2021 American Chemical Society.

Item Type:	Journal Article
Publication:	Journal of Physical Chemistry B
Publisher:	American Chemical Society
Additional Information:	The copyright for this article belongs to American Chemical Society.
Keywords:	Binding energy; Complexation; Free energy; Ketones; Ligands; Molecular dynamics; Polycyclic aromatic hydrocarbons; RNA, Anti-cancer therapeutics; Benzimidazole ligands; Computational studies; G-quadruplex structure; H-bonding interaction; Molecular dynamics simulations; Solvent accessible surface areas; Structure activity relationships, Bioinformatics, guanine quadruplex; ligand; RNA, molecular docking; molecular dynamics; telomere, G-Quadruplexes; Ligands; Molecular Docking Simulation; Molecular Dynamics Simulation; RNA; Telomere
Department/Centre:	Division of Chemical Sciences > Organic Chemistry
Date Deposited:	16 Feb 2023 10:14
Last Modified:	16 Feb 2023 10:14
URI:	https://eprints.iisc.ac.in/id/eprint/80513

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