Conformational search of antisense nucleotides. Part 2

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Organic Chemistry

Background:

• Phosphorotioate nucleotide analogs are crucial in biochemical research.
• Unusual moieties, like chiral P and double-bonded Se atoms, present computational challenges.
• Accurate molecular modeling requires validated force fields.

Purpose of the Study:

• To develop and validate a new set of Molecular Mechanics Force Field (MMFF) parameters for a novel phosphorotioate nucleotide.
• To perform a comprehensive conformational search of the compound's diastereoisomers.
• To validate the developed parameters by comparing computational results with experimental Nuclear Magnetic Resonance (NMR) data.

Main Methods:

• Development of a new MMFF parameter set.
• Application of Monte Carlo and molecular dynamics simulations for conformational searching.
• Comparison of calculated structural properties with NMR measurements.

Main Results:

• Successful parameterization of the phosphorotioate nucleotide compound.
• Identification of the conformational landscape of the diastereoisomers.
• Validation of the new MMFF parameters through experimental data.

Conclusions:

• The developed MMFF parameters accurately describe the novel phosphorotioate nucleotide.
• This parameterization enables reliable conformational analysis of similar compounds.
• The study validates the use of computational methods for characterizing complex nucleotide analogs.