Derivation of class II force fields. VI. Carbohydrate compounds and anomeric effects

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Carbohydrate Chemistry

Background:

• Force fields are essential for molecular simulations.
• Accurate representation of anomeric effects in carbohydrates is challenging.
• Existing class I force fields struggle with carbohydrate systems.

Purpose of the Study:

• To derive and validate a class II force field for acetal, hemiacetal, and carbohydrate compounds.
• To assess the performance of the new force field against ab initio calculations.
• To compare the class II force field with existing class I force fields (CVFF, AMBER) for carbohydrate systems.

Main Methods:

• Generating quantum mechanical energy surfaces for eighteen model compounds.
• Deriving a class II force field and assessing its functional form.
• Performing ab initio calculations (HF/6-31G*) for validation and comparison.
• Analyzing structural, energetic, and dynamic properties, including vibrational frequencies.

Main Results:

• The class II force field accurately reproduces anomeric structural and energetic differences.
• Class I force fields (CVFF, AMBER) show significant deviations (up to 5 kcal/mol) in relative energies.
• Energy component analysis reveals torsional energies dominate anomeric differences in the class II force field.
• The class II force field correctly predicts anomeric and exo-anomeric energy differences for key molecules.

Conclusions:

• The developed class II force field provides a significant improvement for modeling anomeric effects in carbohydrates.
• This new force field enables more accurate simulations of carbohydrate systems.
• The findings highlight the limitations of class I force fields for complex carbohydrate structures.