Phosphorylation effects and molecular mechanisms involved with hDAT and dopamine transport (absorption and efflux) and the interactions with CaMKII

• Grant number: 21/14811-7
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2022
• End date: June 30, 2024
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Ana Lígia Barbour Scott
• Grantee: Ana Lígia Barbour Scott
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

A better comprehension of the molecular mechanisms that take part in several neurodegenerative illnesses (such as Alzheimer and Parkinson's disease, lateral amyotrophic sclerosis, and so on) can aid in the development of new drugs and treatments. One of the main pathologic characteristics present in all of the previously cited disorders is the present of insoluble protein aggregates. For example: Lewy bodies associates with Parkinson's and Lewy bodies dementia. This aggregated are made up mainly by the ±-sinucleína protein which presents a variety of conformations: monomeric and unstructured in physiological solution, multimeric (usually helical tetrameric), and cross-ß -sheet-rich architecture of aggregates. The molecular mechanism and interactions among Dopamine Transporter (DAT), ±-sinucleína and Kinesin play an important role in Dopamine Metabolism at the Nerve Terminals. This project aims to understand the molecular mechanisms involved in transporting dopamine metabolism through simulation techniques using hybrid MDeNM methods that combine NMA (using ENMs or complete atomic models), molecular dynamics and experimental data from biophysical techniques. (AU)