Explicit ions/implicit water generalized Born model for nucleic acids

Journal Article · Fri May 18 00:00:00 EDT 2018 · Journal of Chemical Physics

DOI:https://doi.org/10.1063/1.5027260· OSTI ID:1455301

Tolokh, Igor S. ^[1]; Thomas, Dennis G. ^[2]; Onufriev, Alexey V.  ^[1]

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1. Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States)
2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Computational Biology, Biological Sciences Division

>The ion atmosphere around highly charged nucleic acid molecules plays a significant role in their dynamics, structure, and interactions. Here we utilized the implicit solvent framework to develop a model for the explicit treatment of ions interacting with nucleic acid molecules. The proposed explicit ions/implicit water model is based on a significantly modified generalized Born (GB) model and utilizes a non-standard approach to define the solute/solvent dielectric boundary. Specifically, the model includes modifications to the GB interaction terms for the case of multiple interacting solutes—disconnected dielectric boundary around the solute-ion or ion-ion pairs. A fully analytical description of all energy components for charge-charge interactions is provided. The effectiveness of the approach is demonstrated by calculating the potential of mean force for Na⁺–Cl^– ion pair and by carrying out a set of Monte Carlo (MC) simulations of mono- and trivalent ions interacting with DNA and RNA duplexes. We report the monovalent (Na⁺) and trivalent (CoHex³⁺) counterion distributions predicted by the model are in close quantitative agreement with all-atom explicit water molecular dynamics simulations used as reference. Expressed in the units of energy, the maximum deviations of local ion concentrations from the reference are within k_BT. The proposed explicit ions/implicit water GB model is able to resolve subtle features and differences of CoHex distributions around DNA and RNA duplexes. These features include preferential CoHex binding inside the major groove of the RNA duplex, in contrast to CoHex biding at the “external” surface of the sugar-phosphate backbone of the DNA duplex; these differences in the counterion binding patters were earlier shown to be responsible for the observed drastic differences in condensation propensities between short DNA and RNA duplexes. MC simulations of CoHex ions interacting with the homopolymeric poly(dA·dT) DNA duplex with modified (de-methylated) and native thymine bases are used to explore the physics behind CoHex-thymine interactions. The simulations suggest that the ion desolvation penalty due to proximity to the low dielectric volume of the methyl group can contribute significantly to CoHex-thymine interactions. Compared to the steric repulsion between the ion and the methyl group, the desolvation penalty interaction has a longer range and may be important to consider in the context of methylation effects on DNA condensation.

• Research Organization: Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE; National Institutes of Health (NIH); National Science Foundation (NSF)
• Grant/Contract Number: AC05-76RL01830; R01 GM099450; MCB-1715207
• OSTI ID: 1455301
• Report Number(s): PNNL-SA-134331; 453040220
• Journal Information: Journal of Chemical Physics, Vol. 148, Issue 19; ISSN 0021-9606
• Publisher: American Institute of Physics (AIP)
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
generalized born
nucleic acids
explicit ion model
implicit water model