Mesoscopic model for DNA G-quadruplex unfolding

[EN] Genomes contain rare guanine-rich sequences capable of assembling into four-stranded helical structures, termed G-quadruplexes, with potential roles in gene regulation and chromosome stability. Their mechanical unfolding has only been reported to date by all-atom simulations, which cannot dissect the major physical interactions responsible for their cohesion. Here, we propose a mesoscopic model to describe both the mechanical and thermal stability of DNA G-quadruplexes, where each nucleotide of the structure, as well as each central cation located at the inner channel, is mapped onto a single bead. In this framework we are able to simulate loading rates similar to the experimental ones, which are not reachable in simulations with atomistic resolution. In this regard, we present single-molecule force-induced unfolding experiments by a high-resolution optical tweezers on a DNA telomeric sequence capable of adopting a G-quadruplex conformation. Fitting the parameters of the model to the experiments we find a correct prediction of the rupture-force kinetics and a good agreement with previous near equilibrium measurements. Since G-quadruplex unfolding dynamics is halfway in complexity between secondary nucleic acids and tertiary protein structures, our model entails a nanoscale paradigm for non-equilibrium processes in the cell.Work supported by the Spanish Ministry of Economy and Competitiveness (MINECO), grant No. FIS2014-55867, co-financed by FEDER funds. We also thank the support of the Aragon Government and Fondo Social Europeo to FENOL group. Work in J.R.A.-G. laboratory was supported by a grant from MINECO, No. MAT2015-71806-R).Bergues-Pupo, A.; Gutiérrez, I.; Arias-Gonzalez, JR.; Falo, F.; Fiasconaro, A. (2017). Mesoscopic model for DNA G-quadruplex unfolding. Scientific Reports. 7:1-13. https://doi.org/10.1038/s41598-017-10849-2S1137Arias-Gonzalez, J. R. Single-molecule portrait of DNA and RNA double helices. Integr. 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A computational study of dsDNA pairs and vibrational resonance in separating water

This article investigates the relationship between molecular sequence and dependent interacting behavior of molecular segment pairs and secondly, sequence dependent, vibrational resonance in surrounding normal saline, protein-free water. The development of a molecular model to explore these systems phenomena, the results of several nanoscale molecular dynamics simulations, and analysis of behavior of interacting ΦX174 double-stranded DNA segment pair models in various configurations are presented. Fourier analysis revealed intriguing vibration frequencies within the solvent plane between the segments, while subsequent frequency domain transformation of the time domain waveforms revealed statistically significant resonating harmonic signals in the THz range. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11693-014-9157-3) contains supplementary material, which is available to authorized users

Analysis of Supramolecular Complexes of 3-Methylxanthine with Field Asymmetric Waveform Ion Mobility Spectrometry Combined with Mass Spectrometry

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