Carvalho, JosuéSantos, TiagoCarrilho, RuiSousa, FaniSalgado, GilmarQueiroz, JoãoCruz, Carla2020-01-102020-01-102019Josué 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: 10.1080/07391102.2019.1632743http://hdl.handle.net/10400.6/8190Using 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.engmiRNA 149RNA GquadruplexMolecular dynamicsLigand screeningThermodynamicsjournal article10.1080/07391102.2019.1632743