On the Use of PDB X-Ray Crystal Structures as Force Field Target and Validation Data for Pyranose Ring Puckering

Area of Science:

• Carbohydrate chemistry and structural biology.
• Computational biophysics and molecular modeling.
• Biomolecular force field development and validation.

Background:

• Tetrahydropyran is the core structure of pyranose monosaccharides in vertebrate glycans.
• Monosaccharide ring puckering influences glycan conformation, vital for biomolecular structure and signaling.
• Protein Data Bank (PDB) offers experimental glycan structural data, but conditions differ from biological environments.

Purpose of the Study:

• To assess the utility of PDB X-ray crystal data for developing and validating carbohydrate force fields.
• To compare experimental glycan puckering conformations with simulation data under various conditions.
• To determine the influence of solvent and charge on monosaccharide ring puckering preferences.

Main Methods:

• Extended-system adaptive biasing force (eABF) molecular dynamics simulations were performed.
• Simulations were conducted in both vacuum and explicit aqueous solvent using the CHARMM36 force field.
• Ring puckering conformations from simulations were compared with PDB X-ray crystal data for various monosaccharides.

Main Results:

• For uncharged monosaccharides, simulation puckering preferences (both vacuum and aqueous) strongly correlated with PDB data.
• For charged monosaccharides, only aqueous simulations showed strong correlation with PDB data; vacuum simulations did not.
• This indicates that aqueous simulation environments are essential for accurately modeling charged monosaccharides.

Conclusions:

• PDB X-ray crystal data can be a valuable reference for carbohydrate force field development.
• Aqueous simulation data is critical for accurately capturing the puckering preferences of charged monosaccharides.
• Comparing aqueous simulation puckering data with PDB data is a valid approach for force field validation.