Jump to main content
Jump to site search

Issue 17, 2021
Previous Article Next Article

Molecular mechanism related to the binding of fluorophores to Mango-II revealed by multiple-replica molecular dynamics simulations

Author affiliations

Abstract

Recently, RNA aptamers activating small-molecule fluorophores have been successfully applied to tag and track RNAs in vivo. It is of significance to investigate the molecular mechanism of the fluorophore-RNA aptamer bindings at the atomic level to seek a possible pathway to enhance the fluorescence efficiency of fluorophores. In this work, multiple replica molecular dynamics (MRMD) simulations, essential dynamics (ED) analysis, and hierarchical clustering analysis were coupled to probe the effect of A22U mutation on the binding of two fluorophores, TO1-Biotin (TO1) and TO3-Biotin (TO3), to the Mango-II RNA aptamer (Mango-II). ED analysis reveals that A22U induces alterations in the binding pocket and sites of TO1 and TO3 to the Mango-II, which in turn tunes the fluorophore-RNA interface and changes the interactions of TO1 and TO3 with separate nucleotides of Mango-II. Dynamics analyses also uncover that A22U exerts the opposite impact on the molecular surface areas of the Mango-II and sugar puckers of nucleotides 22 and 23 in Mango-II complexed with TO1 and TO3. Moreover, the calculations of binding free energies suggest that A22U strengthens the binding ability of TO1 to the mutated Mango-II but weakens TO3 to the mutated Mango-II when compared with WT. These findings imply that point mutation in nucleotides possibly tune the fluorescence of fluorophores binding to RNA aptamers, providing a possible scheme to enhance the fluorescence of fluorophores.

Graphical abstract: Molecular mechanism related to the binding of fluorophores to Mango-II revealed by multiple-replica molecular dynamics simulations

Back to tab navigation

Supplementary files

Article information


Submitted
13 Dec 2020
Accepted
14 Apr 2021
First published
15 Apr 2021

Phys. Chem. Chem. Phys., 2021,23, 10636-10649
Article type
Paper

Molecular mechanism related to the binding of fluorophores to Mango-II revealed by multiple-replica molecular dynamics simulations

J. Chen, N. Li, X. Wang, J. Chen, J. Z. H. Zhang and T. Zhu, Phys. Chem. Chem. Phys., 2021, 23, 10636
DOI: 10.1039/D0CP06438F

Social activity

Search articles by author

Spotlight

Advertisements