Predicting
Site-Binding Modes of Ions and Water to
Nucleic Acids Using Molecular Solvation Theory
George
M. Giambaşu
David A. Case
Darrin M. York
10.1021/jacs.8b11474.s001
https://acs.figshare.com/articles/journal_contribution/Predicting_Site-Binding_Modes_of_Ions_and_Water_to_Nucleic_Acids_Using_Molecular_Solvation_Theory/7645253
Site binding of ions and water shapes
nucleic acids folding, dynamics,
and biological function, complementing the more diffuse, nonspecific
“territorial” ion binding. Unlike territorial binding,
prediction of site-specific binding to nucleic acids remains an unsolved
challenge in computational biophysics. This work presents a new toolset
based on the 3D-RISM molecular solvation theory and topological analysis
that predicts cation and water site binding to nucleic acids. 3D-RISM
is shown to accurately capture alkali cations and water binding to
the central channel, transversal loops, and grooves of the <i>Oxytricha nova</i>’s telomeres’ G-quadruplex (<i>Oxy-GQ</i>), in agreement with high-resolution crystallographic
data. To improve the computed cation occupancy along the <i>Oxy-GQ</i> central channel, it was necessary to refine and validate new cation–oxygen
parameters using structural and thermodynamic data available for crown
ethers and ion channels. This single set of parameters that describes
both localized and delocalized binding to various biological systems
is used to gain insight into cation occupancy along the <i>Oxy-GQ</i> channel under various salt conditions. The paper concludes with
prospects for extending the method to predict divalent cation binding
to nucleic acids. This work advances the forefront of theoretical
methods able to provide predictive insight into ion atmosphere effects
on nucleic acids function.
2019-01-11 00:00:00
divalent cation binding
3 D-RISM
acid
Oxy-GQ
ion atmosphere effects
Molecular Solvation Theory Site binding
water site binding
cation occupancy