Development of novel computational protocols to study amyloid oligomerization

开发新的计算协议来研究淀粉样蛋白寡聚化

基本信息

批准号：
10674974
负责人：
Viet Hoang Man
金额：
$ 14.73万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-15 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10674974
关键词：
Abeta synthesis Academy Acetylcholine Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease therapy Alzheimer’s disease biomarker Amyloid Amyloid Proteins Amyloid beta-Protein Artificial Intelligence Authorization documentation Biological Assay Brain Cells Characteristics Clinical Trials Computers Computing Methodologies Data Analyses Dementia Development Development Plans Disease Dissociation Doctor of Philosophy Drug Compounding Drug Screening Education Environment Equipment Faculty Fellowship Focused Ultrasound Focused Ultrasound Therapy Frequencies Goals Grant Huntington Disease In Vitro Kinetics Lasers Leadership Learning Light Machine Learning Mentors Methods Molecular Multicenter Studies Natural Compound Natural Products Neurodegenerative Disorders Neurons Outcome Parkinson Disease Pathologic Pathologic Processes Peptides Pharmaceutical Preparations Pharmacologic Substance Pharmacy Schools Phototherapy Physical therapy Physics Polishes Postdoctoral Fellow Prevention Process Program Development Protocols documentation Radiation Research Research Activity Research Personnel Research Proposals Resources Schools Science Scientist Side Signal Transduction Statistical Data Interpretation Statistical Methods Structure Symptoms System Testing Training Training Activity Ultrasonic wave Universities Validation abeta accumulation abeta oligomer amyloid formation base career career development data access data resource design experimental study fighting improved inhibitor injured innovation insight man member molecular dynamics molecular scale monomer novel prevent protein aggregation rational design simulation skills small molecule targeted treatment tau Proteins tau aggregation therapeutically effective treatment optimization ultrasound virtual virtual screening

项目摘要

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”.

项目摘要越南博士是一位生物物理学家，其总体职业目标是防止发展与淀粉样蛋白/肽聚集有关的神经退行性疾病。他获得了他的博士学位波兰科学院（IFPAN）物理学研究所的物理学学位。他在加入了药学系之前，完成了两项博士后奖学金匹兹堡大学药学院（Pittpharmacy）是科学家。研究建议标题为 “研究淀粉样蛋白寡聚的新型计算方案的制定”结合了分子动力学（MD）模拟集成的创新系统设计和特殊数据分析，高级统计方法和科学编程开发，以研究淀粉样蛋白的寡聚化蛋白质/肽，以鉴定形成淀粉样蛋白低聚物的抑制剂，并建立理论靶向消除有毒淀粉样蛋白低聚物的物理疗法的基础。研究建议包括三个目的：1）研究淀粉样蛋白/肽的寡聚； 2）识别从认可的药物和天然化合物形成淀粉样蛋白有毒寡聚的抑制剂； 3）研究以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，提供潜在的药物和有希望的物理防止帕金森氏病和阿尔茨海默氏病等某些疾病的疗法疾病都与淀粉样蛋白寡聚有关。拟议的职业发展计划建立在他以前的训练中，并具有四个训练目标，以增强他成为一个轨迹独立研究者：1）用于淀粉样蛋白的实验方法中的经验和教学学习聚合; 2）获取和应用高级统计分析，机器学习以及人工智力; 3）成为力领域和科学计划发展的专家； 4）发展执行多中心研究的领导和专业技能。 Man博士和他的主要导师Junmei Wang博士，已经组建了一支强大的联席会员团队顾问通过拟议的培训和研究活动来指导越野博士。拟议的职业开发计划利用了通过匹兹堡大学的Pittpharmacy和其他学校/中心。 Pittpharmacy致力于通过内部赠款，行政支持和结构化为初级人员和教职员工提供支持网络和教育的机会。 Man博士将获得高性能的计算机资源摘自Pittresearch“研究计算中心”（https://crc.pitt.edu/）和王博士的小组。他还将获得Xie博士小组的访问与痴呆症疾病有关的数据的许可洛佩兹博士的“阿尔茨海默氏病研究中心”。