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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 多尺度分子模拟方法将用于了解抗体聚集背后的机制。随后将设计防止这种聚集的方法，从而使我们能够获得可用于治疗癌症的单克隆抗体的稳定的浓缩水溶液。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种分子模拟工具，可以预测的基础上的抗体结构的聚集机制。获得对聚集的详细的机械理解将为合理设计防止聚集的方法铺平道路，而不是目前的试错方法。

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.