STRUCTURAL BASIS FOR IMMUNOGENICITY OF N MENINGITIDIS CAPSULAR POLYSACCHARIDES

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。脑膜炎奈瑟氏菌的胶囊由碳水化合物聚合物组成，这些聚合物在有机体周围形成细胞壁。它们在表面的战略位置使它们成为毒力和侵袭性的关键决定因素，因此成为宿主免疫系统的目标。准确表示多糖的三维结构和构象行为是使其与抗体相互作用的特异性和抗原性合理化所必需的。我们在GLYCAM系列力场中开发了一组参数，用于CPS半抗原-抗体相互作用的凝聚相计算研究。还实施了一种新的方法，包括调整GLYCAM扭转项和执行简短、显式的溶剂MD模拟，以重现代表脑膜炎奈瑟菌BA型半抗原的模型化合物的实验溶液构象群体。这些新参数能够重现核磁共振实验数据，如标量J偶联、NOE和旋转异构体数量。

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.