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 Resea...