Ion binding to quadruplex DNA stems. Comparison of MM and QM descriptions reveals sizable polarization effects not included in contemporary simulations

Gkionis, Konstantinos, Kruse, Holger, Platts, James Alexis ORCID: https://orcid.org/0000-0002-1008-6595, Mladek, Arnost, Koca, Jaroslav and Sponer, Jiri 2014. Ion binding to quadruplex DNA stems. Comparison of MM and QM descriptions reveals sizable polarization effects not included in contemporary simulations. Journal of Chemical Theory and Computation 10 (3) , pp. 1326-1340. 10.1021/ct4009969

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Abstract

Molecular mechanical (MM) force fields are commonly employed for biomolecular simulations. Despite their success, the non-polarizable nature of contemporary additive force fields limits their performance, especially in long simulations and when strong polarization effects are present. Guanine quadruplex D(R)NA molecules have been successfully studied by MM simulations in the past. However, the G-stems are stabilized by a chain of monovalent cations which create sizable polarization effects. Indeed, simulation studies revealed several problems which have been tentatively attributed to the lack of polarization. Here we provide a detailed comparison between quantum-chemical (QM) DFT-D3 and MM Potential Energy Surfaces of ion binding to G-stems and assess differences which may affect MM simulations. We suggest that MM describes binding of a single ion to the G-stem rather well. However, polarization effects become very significant when a second ion is present. We suggest that the MM approximation substantially limits accuracy of description of energy and dynamics of multiple ions inside the G-stems and binding of ions at the stem-loop junctions. The difference between QM and MM descriptions is also explored using symmetry-adapted perturbation theory and Quantum Theory of Atoms in Molecules analyses, which reveal delicate balance of electrostatic and induction effects.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Subjects:	Q Science > QD Chemistry
Publisher:	American Chemical Society
ISSN:	1549-9618
Last Modified:	25 Oct 2022 09:07
URI:	https://orca.cardiff.ac.uk/id/eprint/57294

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