STRUCTURAL BASIS FOR IMMUNOGENICITY OF N MENINGITIDIS CAPSULAR POLYSACCHARIDES

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The capsules of the Neisseria meningitidis bacteria consist of carbohydrate polymers which form cell walls around the organisms. Their strategic location at the surface makes them key determinants of virulence and invasiveness, and thus are targeted by the host's immune system. Accurate representation of the three-dimensional structures and conformational behaviour of the polysaccharides is required to rationalize the specificity and antigenicity of their interactions with antibodies. We have developed a set of parameters in the GLYCAM series of force fields for condensed-phase computational studies of CPS hapten-antibody interactions. A new approach has also been implemented which involves adjusting the GLYCAM torsion terms and performing short, explicity solvent MD simulations in order to reproduce experimental solution conformer populations of the model compounds representing haptens of N. meningitidis serotype BA. These new parameters are able to reproduce experimental NMR data such as scalar J-couplings, NOEs, and rotamer populations.