MULTI-SCALE MODELING OF THERAPEUTIC ANTIBODIES: MOLECULAR MECHANISMS FOR AGGREG

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 多尺度分子模拟方法将被用来理解抗体聚集背后的机制。接下来将设计防止这种聚集的方法，从而使我们能够获得稳定、浓缩的用于癌症治疗的单抗的水溶液。这项研究还有助于了解导致II型糖尿病和阿尔茨海默氏症等神经退行性疾病的蛋白质聚集背后的机制。最终，我们的目标是开发一个分子模拟工具，可以基于抗体体系结构预测聚集机制。获得对聚集的详细的机械性理解将为合理设计防止聚集的方法铺平道路，而不是目前的试验和错误方法。

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. Multi-scale molecular simulation methods will be used to understand the mechanism behind antibody aggregation. This will be followed by designing ways to prevent such aggregation, thus enabling us to obtain stable, concentrated aqueous solutions of monoclonal antibodies useful in the treatment of cancer. The study also helps in understanding mechanism behind protein aggregation that cause type II diabetes and neurodegenerative diseases such as Alzheimers. Ultimately, we aim to develop a molecular simulation tool that can predict the mechanism for aggregation based on the antibody architecture. Gaining a detailed mechanistic understanding of aggregation will pave the way towards rational design of approaches for prevention of aggregation as opposed to the current trial and error approaches.