Effect of backbone chemistry on hybridization thermodynamics of oligonucleic acids: a coarse-grained molecular dynamics simulation study

Soft Matter
Ahmadreza F Ghobadi, Arthi Jayaraman

Abstract

In this paper we study how varying oligonucleic acid backbone chemistry affects the hybridization/melting thermodynamics of oligonucleic acids. We first describe the coarse-grained (CG) model with tunable parameters that we developed to enable the study of both naturally occurring oligonucleic acids, such as DNA, and their chemically-modified analogues, such as peptide nucleic acids (PNAs) and locked nucleic acids (LNAs). The DNA melting curves obtained using such a CG model and molecular dynamics simulations in an implicit solvent and with explicit ions match with the melting curves obtained using the empirical nearest-neighbor models. We use these CG simulations to then elucidate the effect of backbone flexibility, charge, and nucleobase spacing along the backbone on the melting curves, potential energy and conformational entropy change upon hybridization and base-pair hydrogen bond residence time. We find that increasing backbone flexibility decreases duplex thermal stability and melting temperature mainly due to increased conformational entropy loss upon hybridization. Removing charges from the backbone enhances duplex thermal stability due to the elimination of electrostatic repulsion and as a result a larger energetic gai...Continue Reading

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Citations

Sep 7, 2016·The Journal of Physical Chemistry. B·Ahmadreza F Ghobadi, Arthi Jayaraman
Oct 24, 2017·Soft Matter·Fernando Vargas-LaraJack F Douglas
Sep 14, 2018·Chembiochem : a European Journal of Chemical Biology·Ilaria FurlanKira Astakhova
May 22, 2019·Soft Matter·Daniel J Beltran-VillegasArthi Jayaraman
Sep 29, 2019·Nanoscale·Huihui KuangEfrosini Kokkoli
Dec 11, 2020·Nucleic Acids Research·Asem AlenaizanAnton S Petrov
Mar 2, 2021·The Journal of Physical Chemistry. B·Shizhao LuArthi Jayaraman
Feb 8, 2018·The Journal of Physical Chemistry. B·Joshua E Condon, Arthi Jayaraman
Jun 3, 2020·Journal of Chemical Theory and Computation·Zijie WuArthi Jayaraman
Sep 12, 2020·Biomacromolecules·Heidi R CulverChristopher N Bowman

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