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

• Published in: Journal of chemical theory and computation 2017-08, Vol.13 (8), p.3911-3926
• Main Authors: Havrila, Marek, Stadlbauer, Petr, Islam, Barira, Otyepka, Michal, Šponer, Jiří
• Format: Article
• Language: English
• Subjects: Bifurcations; Cations; Cations, Monovalent - chemistry; Computer simulation; Deformation; Deoxyribonucleic acid; DNA; DNA - chemistry; Dynamic stability; Dynamic structural analysis; Fluid dynamics; G-Quadruplexes; Guanine - chemistry; Mathematical models; Model testing; Molecular chains; Molecular dynamics; Molecular Dynamics Simulation; Nucleic Acid Conformation; Parameterization; Parameters; Physical simulation; Potassium - chemistry; Ribonucleic acid; RNA; RNA - chemistry; Simulation; Sodium - chemistry; Stability analysis; Structural stability; Water - chemistry
• ISSN: 1549-9618; 1549-9626
• DOI: 10.1021/acs.jctc.7b00257

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.