Nucleotides containing variously modified sugars: energetics, structure, and mechanical properties.

Area of Science:

• Computational chemistry
• Molecular modeling
• Biochemistry

Background:

• 2'-deoxyribonucleotide-5'-monophosphates (dNs) are fundamental DNA building blocks.
• Understanding sugar modifications is key to controlling DNA structure and function.
• Existing research lacks comprehensive analysis of modification impacts on dN energetics and mechanics.

Purpose of the Study:

• To investigate the effects of fourteen sugar residue modifications on dN properties.
• To analyze how modifications influence energetic and conformational states (AI and BI).
• To evaluate the impact of modifications on glycosidic bond strength and mechanical stability.

Main Methods:

• Utilized modern quantum chemical approaches for analysis.
• Focused on AI and BI conformations relevant to double-helical DNA.
• Employed implicit solvent models to simulate aqueous solutions.
• Calculated relaxed force constants (RFC) and vibrational root-mean-square (VRMS) deviations.

Main Results:

• Most modifications stabilize either the AI or BI conformation.
• Many modifications significantly strengthen glycosidic bonds, increasing resistance to abasic lesions.
• The CF2 group and 2'-α-fluorine atom showed the most significant glycosidic bond reinforcement.
• A strong correlation exists between dN mechanical properties and energetic characteristics.

Conclusions:

• Sugar modifications offer a tool to reduce structural polymorphism in nucleic acids.
• Modified dNs can be designed for specific structural features and enhanced stability.
• Energetic favorability of conformers is linked to mechanical properties like RFC(δ).