Competition between Stacking and Divalent Cation-Mediated Electrostatic Interactions Determines the Conformations of...

Area of Science:

• Computational biophysics
• Molecular modeling of DNA-protein interactions

Background:

• Divalent cations (Mg2+, Ca2+) and stacking interactions are crucial for DNA stability and phase separation.
• Quantitative models are needed to understand ion-DNA interactions in nucleic acids.
• Existing methods may mask specific ion behaviors.

Purpose of the Study:

• To develop a sequence-dependent computational model (TIS-ION) for simulating ion-DNA interactions.
• To quantitatively compare model predictions with experimental ion-counting and scattering data.
• To elucidate the distinct binding preferences of Mg2+ and Ca2+ to DNA.

Main Methods:

• Development of the TIS-ION computational model incorporating monovalent and divalent ions.
• Simulations of double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) sequences (dA30, dT30).
• Calculation of ion excess numbers, small-angle X-ray scattering (SAXS) profiles, and analysis of ion binding sites.

Main Results:

• The TIS-ION model accurately predicts ion numbers around DNA, matching experimental ion-counting data.
• Calculated SAXS profiles from all-atom structures agree well with experimental results.
• Mg2+ binds to minor grooves and phosphates, while Ca2+ shows specific minor groove binding; both prefer minor over major grooves.

Conclusions:

• The TIS-ION model provides quantitative insights into ion-DNA interactions, validating against experiments.
• Distinct binding behaviors of Mg2+ and Ca2+ to DNA minor grooves were identified.
• The model's success opens avenues for studying DNA biophysics problems involving ion effects.