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

治疗性抗体的多尺度建模：聚集的分子机制

• 批准号: 7723257
• 负责人: BERNHARDT L TROUT
• 金额: $ 0.05万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723257
• 关键词: Antibodies; Architecture; Computer Retrieval of Information on Scientific Projects Database; Funding; Grant; Institution; Methods; Molecular; Monoclonal Antibodies; Neurodegenerative Disorders; Non-Insulin-Dependent Diabetes Mellitus; Prevention approach; Research; Research Personnel; Resources; Solutions; Source; Therapeutic antibodies; United States National Institutes of Health; aqueous; base; cancer therapy; design; molecular scale; multi-scale modeling; prevent; protein aggregation; simulation; tool

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 多尺度分子模拟方法将用于了解抗体聚集的机制。随后将设计防止这种聚集的方法，从而使我们能够获得稳定的，浓缩的单克隆抗体水溶液，可用于治疗癌症。该研究还有助于理解引起II型糖尿病和神经退行性疾病（如阿尔茨海默氏症）的蛋白质聚集背后的机制。最终，我们旨在开发一个分子模拟工具，该工具可以根据抗体结构来预测聚集机制。与当前的试验和错误方法相反，获得对聚合的详细机械理解将为预防聚集的方法的理性设计铺平道路。