G-quadruplexes (GQs) are key noncanonical DNA and RNA architectures stabilized by desolvated monovalent cations present in their central channels. We analyze extended atomistic molecular dynamics simulations (∼580 μs in total) of GQs with 11 monovalent cation parametrizations, assessing GQ overall structural stability, dynamics of internal cations, and distortions of the G-tetrad geometries. Majority of simulations were executed with the SPC/E water model; however, test simulations with TIP3P and OPC water models are also reported. The identity and parametrization of ions strongly affect behavior of a tetramolecular d[GGG]4 GQ, which is unstable with several ion parametrizations. The remaining studied RNA and DNA GQs are structurally stable, though the G-tetrad geometries are always deformed by bifurcated H-bonding in a parametrization-specific manner. Thus, basic 10-μs-scale simulations of fully folded GQs can be safely done with a number of cation parametrizations. However, there are parametrization-specific differences and basic force-field errors affecting the quantitative description of ion-tetrad interactions, which may significantly affect studies of the ion-binding processes and description of the GQ folding landscape. Our d[GGG]4 simulations indirectly suggest that such studies will also be sensitive to the water models. During exchanges with bulk water, the Na+ ions move inside the GQs in a concerted manner, while larger relocations of the K+ ions are typically separated. We suggest that the Joung-Cheatham SPC/E K+ parameters represent a safe choice in simulation studies of GQs, though variation of ion parameters can be used for specific simulation goals.

CEITEC Central European Institute of Technology Masaryk University Campus Bohunice Kamenice 5 625 00 Brno Czech Republic

Institute of Biophysics Academy of Sciences of the Czech Republic Královopolská 135 612 65 Brno Czech Republic

Regional Centre of Advanced Technologies and Materials Department of Physical Chemistry Faculty of Science Palacky University 17 listopadu 12 771 46 Olomouc Czech Republic

Erratum In

J Chem Theory Comput. 2018 Mar 13;14(3):1820. doi: 10.1021/acs.jctc.8b00011. PubMed

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