Comparative simulation of pneumococcal serogroup 19 polysaccharide repeating units with two carbohydrate force fields

Area of Science:

• Microbiology
• Immunology
• Computational Chemistry

Background:

• Streptococcus pneumoniae causes invasive pneumococcal disease (IPD) in children.
• PCV7 vaccine reduced IPD, but non-vaccine serotypes like 19A have increased.
• PCV7 shows only 26% effectiveness against 19A IPD, despite 19F presence in the vaccine.

Purpose of the Study:

• To investigate the conformational and dynamic differences between 19F and 19A pneumococcal polysaccharide repeating units.
• To understand the molecular basis for the low cross-protection of PCV7 against 19A serotype infections.

Main Methods:

• 100ns aqueous molecular dynamics simulations of di- and trisaccharide components.
• Comparison of free energy surfaces for glycosidic linkages.
• Utilized both CHARMM and GLYCAM carbohydrate force fields for calculations.

Main Results:

• Both CHARMM and GLYCAM force fields predicted distinct conformational behaviors for 19F and 19A polysaccharides.
• The 19F repeating unit exhibited a wider range of conformation families compared to the more restricted 19A trisaccharide.
• Key differences were identified between the force fields, but overall trends were consistent.

Conclusions:

• A probable conformational difference exists between 19F and 19A polysaccharides.
• This conformational disparity likely explains the limited cross-protection of PCV7 vaccines against 19A invasive pneumococcal disease.