Harmonizing Interstrand Electrostatic Repulsion by Conformational Rigidity in Counterion-Deprived Z-DNA: A Molecular...

Area of Science:

• Molecular Biology
• Biochemistry
• Structural Biology

Background:

• Deoxyribonucleic acid (DNA) exists in various forms, including the common B-DNA and noncanonical structures like Z-DNA.
• Z-DNA has been implicated in diseases such as cancer and autoimmune disorders.
• Understanding Z-DNA's stability is crucial for its potential therapeutic applications.

Purpose of the Study:

• To evaluate the conformational stability of locked-sugar-based Z-DNA.
• To investigate the structural and energetic factors contributing to Z-DNA stability.
• To explore the potential of modified Z-DNA constructs in medicinal applications and advanced modeling.

Main Methods:

• All-atom explicit-solvent molecular dynamics simulations were employed.
• Conformational stability was assessed in the presence and absence of counterions.
• Structural and energetic analyses were conducted to understand stability mechanisms.

Main Results:

• Locked-sugar Z-DNA maintained its left-handed conformation even without counterions.
• Structural rigidity in the modified DNA overcame electrostatic repulsion between strands.
• Control Z-DNA without counterions rapidly unfolded, highlighting the stability of the modified form.

Conclusions:

• Modified Z-DNA exhibits remarkable conformational stability, even in low-salt conditions.
• Backbone widening and enhanced inter-strand electrostatics likely contribute to this stability.
• The designed Z-DNA construct offers a stable model for studying Z-DNA and may have therapeutic and biotechnological potential.