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Advisor(s)
Abstract(s)
Using a molecular dynamics approach, the study of the interaction between six different known ligands and a predicted pre-miRNA 149 RNA G-quadruplex (rG4) structure is reported. The stabilization of rG4 structures formed within the pre-miRNA stem-loop regions using small ligands is an attractive anticancer strategy. Particularly, miRNA-149 is upregulated in a variety of cancers such as prostate cancer and is therefore a potential target for drug development. The results show that ligands C8 and PhenDC3 interact with the rG4 structure via stacking interactions with the end G-quartets. Ligands [16]phenN2, [32]phen2N4 and pyridostatin on the other hand bind the loops/groove interface of the rG4 being H-bonding and electrostatic interactions the driving force of the interaction. The C8 precursor, C8-NH2, emphasizes the structural nuances of the rG4 short loops as the lack of a large terminal aromatic moiety produced a mixed stacking-groove binding mode. Overall, this study may help the design of specific ligands for pre-miRNA rG4 towards anticancer therapeutics development. Communicated by Ramaswamy H. Sarma.
Description
Keywords
miRNA 149 RNA Gquadruplex Molecular dynamics Ligand screening Thermodynamics
Citation
Josué Carvalho, Tiago Santos, Rui Carrilho, Fani Sousa, Gilmar F. Salgado, João António Queiroz & Carla Cruz (2019): Ligand screening to pre-miRNA 149 G-quadruplex investigated by molecular dynamics, Journal of Biomolecular Structure and Dynamics, DOI: 10.1080/07391102.2019.1632743
Publisher
Taylor & Francis