Development of novel computational protocols to study amyloid oligomerization

项目摘要 博士Viet Man是一位生物制药学家，其首要职业目标是防止 与淀粉样蛋白/肽聚集相关的神经变性疾病。他 获得博士学位波兰科学院物理研究所物理学学位。他 完成了两个博士后奖学金，然后加入药物科学系在 匹兹堡大学药学院（PittPharmacy）担任科学家。该研究计划题为 “开发新的计算方案来研究淀粉样蛋白寡聚化”结合了分子 动力学（MD）模拟集成了创新的系统设计和特殊的数据分析，先进的 淀粉样蛋白寡聚化的统计学方法和科学规划的发展 蛋白质/肽，以鉴定淀粉样蛋白低聚物形成的抑制剂，并建立理论 物理治疗的基础，目标是消除有毒的淀粉样蛋白低聚物。研究 该计划包括三个目标：1）研究淀粉样蛋白/肽的寡聚化; 2）鉴定 用于由批准的药物和天然化合物形成淀粉样蛋白毒性低聚物的抑制剂; 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 淀粉样蛋白寡聚化过程的重要见解，提供了潜在的药物和有前途的物理 用于预防某些疾病如帕金森病和阿尔茨海默病的发展的疗法 疾病，这两者都与淀粉样蛋白寡聚化有关。拟议职业发展计划 是建立在他以前的训练与四个训练目标，以提高他的轨迹成为一个 独立研究者：1）用于淀粉样蛋白的实验方法的经验和教学学习 2）获取和应用先进的统计分析，机器学习以及人工智能 情报; 3）成为力场和科学计划开发方面的专家; 4）开发 执行多中心研究的领导能力和专业技能。 博士曼和他的主要导师王俊梅博士，组建了一个强大的共同导师团队， 此外，还将邀请一些顾问指导Viet博士开展拟议的培训和研究活动。提议的职业 发展计划利用知识，设备和数据资源，通过 PittPharmacy和匹兹堡大学的其他学校/中心。PittPharmacy致力于 通过内部赠款，行政支持和结构化的支持初级工作人员和教职员工 网络和教育的机会。文博士将获得高性能的计算机资源 来自PittResearch“研究计算中心”（https：//crc.pitt.edu/）和王博士的小组。他 我也将从谢博士的小组获得访问痴呆症相关数据的许可 和洛佩斯博士的“老年痴呆症研究中心”。

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”.