Conformational search of antisense nucleotides

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Organic Chemistry

Background:

• Accurate molecular modeling requires precise atom parameters.
• Selenium-containing nucleosides are of interest in various chemical and biological applications.
• Existing molecular mechanics force fields may lack parameters for selenium.

Purpose of the Study:

• To report a preliminary implementation of Modified Molecular Mechanics Force Field (MMFF) parameters for selenium atoms.
• To enable accurate modeling of nucleoside structures containing selenium.
• To provide a computational tool for studying selenium-containing nucleosides.

Main Methods:

• Utilized X-ray crystallographic structures of selenium-containing nucleosides (compounds 1 and 2) as reference data.
• Employed ab initio quantum mechanical methods to analyze torsional energy profiles and charge distributions.
• Performed Monte Carlo simulations and energy minimization in a solvation model to explore conformational space.

Main Results:

• Developed and validated preliminary MMFF parameters for selenium atoms.
• Confirmed the accuracy of the parameters by comparing computational predictions with experimental X-ray data.
• Characterized the torsional energy landscape and charge distribution of the modeled nucleosides.
• Identified preferred conformations through solvation-based energy minimization.

Conclusions:

• The implemented selenium atom parameters provide a foundation for accurate molecular modeling of nucleosides.
• Computational methods, including ab initio and Monte Carlo simulations, are crucial for parameter validation and conformational analysis.
• This work facilitates further investigation into the structure-activity relationships of selenium-containing nucleosides.