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Title: Explicit ions/implicit water generalized Born model for nucleic acids

Abstract

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 defining 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. 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 (PMF) 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. 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 kBT. The proposed explicit ions/implicit water GB modelmore » 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 RNA duplex, in contrast to CoHex biding at the "external" surface of the sugar-phosphate backbone of DNA duplex; these differences in the counterion binding patters were shown earlier to be responsible for the observed drastic differences in condensation propensities between short DNA and RNA duplexes. MC simulations of CoHex ions interacting with 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.« less

Authors:
 [1];  [2]; ORCiD logo [3]
  1. Department of Computer Science, Virginia Tech, Blacksburg, Virginia 24061, USA
  2. Computational Biology, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, USA
  3. Departments of Computer Science and Physics, Center for Soft Matter and Biological Physics, Virginia Tech, Blacksburg, Virginia 24061, USA
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1455301
Report Number(s):
PNNL-SA-134331
Journal ID: ISSN 0021-9606; 453040220
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Chemical Physics; Journal Volume: 148; Journal Issue: 19
Country of Publication:
United States
Language:
English
Subject:
generalized born; nucleic acids; explicit ion model; implicit water model

Citation Formats

Tolokh, Igor S., Thomas, Dennis G., and Onufriev, Alexey V.. Explicit ions/implicit water generalized Born model for nucleic acids. United States: N. p., 2018. Web. doi:10.1063/1.5027260.
Tolokh, Igor S., Thomas, Dennis G., & Onufriev, Alexey V.. Explicit ions/implicit water generalized Born model for nucleic acids. United States. doi:10.1063/1.5027260.
Tolokh, Igor S., Thomas, Dennis G., and Onufriev, Alexey V.. Mon . "Explicit ions/implicit water generalized Born model for nucleic acids". United States. doi:10.1063/1.5027260.
@article{osti_1455301,
title = {Explicit ions/implicit water generalized Born model for nucleic acids},
author = {Tolokh, Igor S. and Thomas, Dennis G. and Onufriev, Alexey V.},
abstractNote = {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 defining 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. 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 (PMF) 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. 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 kBT. 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 RNA duplex, in contrast to CoHex biding at the "external" surface of the sugar-phosphate backbone of DNA duplex; these differences in the counterion binding patters were shown earlier to be responsible for the observed drastic differences in condensation propensities between short DNA and RNA duplexes. MC simulations of CoHex ions interacting with 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.},
doi = {10.1063/1.5027260},
journal = {Journal of Chemical Physics},
number = 19,
volume = 148,
place = {United States},
year = {Mon May 21 00:00:00 EDT 2018},
month = {Mon May 21 00:00:00 EDT 2018}
}