DFT application in conformational determination of cellobiose

Area of Science:

• Carbohydrate Chemistry
• Computational Chemistry
• Biophysics

Background:

• Beta-cellobiose is a disaccharide relevant to carbohydrate structure and function.
• Understanding its conformational landscape in aqueous solution is crucial for predicting its behavior.

Purpose of the Study:

• To investigate the potential energy surface of beta-cellobiose in water.
• To identify stable conformations and their governing interactions.
• To explore the utility of NMR chemical shifts for conformational analysis.

Main Methods:

• Density Functional Theory (DFT) calculations were employed to map the potential energy surface.
• Molecular dynamics simulations with 52 water molecules were used to assess solvation effects.
• Nuclear Magnetic Resonance (NMR) chemical shift calculations were performed to correlate shifts with conformations.

Main Results:

• Three distinct energy minima (syn-ϕ/syn-ψ, anti-ϕ/syn-ψ, syn-ϕ/anti-ψ) were identified for beta-cellobiose.
• Hydrogen bonding and H...H repulsion were found to be critical factors in energy variations.
• Significant changes in geometry were observed upon solvation.
• NMR chemical shifts for C4 and C1' atoms were sensitive to conformational changes, providing a fingerprint for each minimum.
• Chemical shielding tensor analysis revealed distinct variations for C1' and C4 atoms across different conformations.

Conclusions:

• The study successfully mapped the conformational space of beta-cellobiose in water.
• NMR chemical shifts serve as reliable indicators for distinguishing between beta-cellobiose conformations.
• The findings provide a basis for using NMR spectroscopy to determine (ϕ, ψ) dihedral angles in related carbohydrate systems.