Development of novel computational protocols to study amyloid oligomerization

项目摘要 越南博士是一位生物物理学家，他的首要职业目标是防止 与淀粉样蛋白/多肽聚集有关的神经退行性疾病。他 获得波兰科学院物理研究所(IFPAN)物理学博士学位。他 在加入药学系之前完成了两个博士后奖学金 匹兹堡大学药学院(PittPharmacy)为科学家。这项研究提案题为 《研究淀粉样蛋白齐聚的新计算方法的发展》结合了分子 动力学(MD)模拟集成创新的系统设计和特殊数据分析，高级 研究淀粉样蛋白齐聚的统计方法和科学编程进展 蛋白质/多肽，以确定淀粉样寡聚体形成的抑制剂，并建立理论 以消除有毒淀粉样寡聚体为目标的物理疗法的基础。这项研究 建议包括三个目标：1)研究淀粉样蛋白/多肽的寡聚；2)鉴定 从批准的药物和天然化合物中抑制淀粉样蛋白毒性低聚物的形成；3) 研究消除有毒低聚物的物理疗法。这些目标的完成将揭示 淀粉样蛋白寡聚过程的重要见解，提供了潜在的药物和前景广阔的物理 预防帕金森氏病和阿尔茨海默氏症等疾病的治疗方法 疾病，这两者都与淀粉样寡聚化有关。拟议的职业发展计划 是建立在他之前的训练基础上的，有四个训练目标，以增强他成为一名 独立调查者：1)淀粉样蛋白实验方法中的经验性和指导性学习 聚合；2)获取和应用高级统计分析、机器学习以及人工智能 智能；3)成为武力领域和科学程序开发方面的专家；4)开发 执行多中心研究的领导力和专业技能。 曼博士和他的主要导师王俊梅博士组建了一支强大的联合导师团队，并 指导越南博士完成拟议的培训和研究活动的顾问。计划中的职业 发展计划利用通过 匹兹堡大学药房和其他学校/中心。PittPharmacy致力于 通过内部拨款、行政支持和结构化支持支持初级员工和教职员工 网络和教育的机会。曼博士将获得高性能的计算机资源 来自皮特研究中心的“研究计算中心”(https://crc.pitt.edu/)和王博士的团队。他 还将获得访问谢博士小组中与痴呆症相关的数据的权限 以及洛佩兹博士的“阿尔茨海默氏症研究中心”。

Project Summary Dr. Viet Man is a biophysicist whose overarching career goal is to prevent the development of neurodegenerative diseases which are associated to the aggregation of amyloid proteins/peptides. He received his Ph.D. degree in physics from Institute of Physics, Polish Academy of Sciences (IFPAN). He completed two postdoctoral fellowships before joining the Department of Pharmaceutical Sciences at The University of Pittsburgh School of Pharmacy (PittPharmacy) as a scientist. The research proposal entitled “Development of Novel Computational Protocols to Study Amyloid Oligomerization” combines Molecular Dynamics (MD) simulation integrated innovative system designs and special data analysis, advanced statistical methods and scientific programming development to investigate the oligomerization of amyloid proteins/peptides, to identify inhibitors for the formation of amyloid oligomers, and to establish theoretical bases for physical therapies that target the elimination of the toxic amyloid oligomers. The research proposal includes three aims: 1) investigate the oligomerization of amyloid proteins/peptides; 2) identify inhibitors for the formation of amyloid toxic oligomers from approved drugs and natural compounds; 3) study physical therapies for eliminating the toxic oligomers. The completion of these aims will reveal important insights of the amyloid oligomerization process, provide potential drugs and promising physical therapies for preventing the development of some diseases such as Parkinson’s disease and Alzheimer's disease, which are both associated to the amyloid oligomerization. The proposed career development plan is built upon his previous training with four training goals to enhance his trajectory toward becoming an independent investigator: 1) Experiential and didactic learning in experimental methods used for amyloid aggregation; 2) Acquire and apply advanced statistical analyses, machine learning as well as artificial intelligence; 3) Become an expert in force field and scientific program development; and 4) Develop leadership and professional skills to execute multicenter studies. Dr. Man and his primary mentor, Junmei Wang, Ph.D., have assembled a strong team of co-mentors and advisors to guide Dr. Viet through the proposed training and research activities. The proposed career development plan utilizes the intellectual, equipment and data resources available through the PittPharmacy and other schools/centers of the University of Pittsburgh. PittPharmacy is committed to supporting junior staff and faculty members through internal grants, administrative support and structured opportunities for networking and education. Dr. Man will obtain the high performant computer resources from the PittResearch “Center for Research Computing” (https://crc.pitt.edu/) and Dr. Wang’s group. He will also obtain the permission for accessing the data related to dementia diseases from Dr. Xie’s group and Dr. Lopez’s “Alzheimer's Disease Research Center”.