Effect of Monovalent Ion Parameters on Molecular Dynamics Simulations of G-Quadruplexes

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Authors	HAVRILA Marek STADLBAUER P. ISLAM B. OTYEPKA M. ŠPONER Jiří
Year of publication	2017
Type	Article in Periodical
Magazine / Source	Journal of Chemical Theory and Computation
MU Faculty or unit	Central European Institute of Technology
Citation
Web	https://pubs.acs.org/doi/abs/10.1021/acs.jctc.7b00257
Doi	http://dx.doi.org/10.1021/acs.jctc.7b00267
Keywords	TELOMERIC G-QUADRUPLEX; AMBER FORCE-FIELD; NUCLEIC-ACID QUADRUPLEXES; KIT PROMOTER QUADRUPLEX; PARTICLE MESH EWALD; GUANINE-QUADRUPLEX; CRYSTAL-STRUCTURE; DNA QUADRUPLEXES; THERMODYNAMIC ANALYSIS; COMPUTER-SIMULATIONS
Description	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 (similar to 580 mu s 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 however, test simulations with TIP3P and OPC water models simulations were executed with the SPC/E water model; 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-mu s-scale simulations of fully folded GQs can be safely done with a number of cation,parametrization. However, there are patametrization-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.
Related projects:	CEITEC 2020