Exploring the Amyloid-beta Aggregation Energy Landscape

• Grant number: 25/03001-5
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2027
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Vitor Barbanti Pereira Leite
• Grantee: Vitor Barbanti Pereira Leite
• Principal researcher abroad: Min-Yeh Tsai
• Institution abroad: National Chung Cheng University, Taiwan
• Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 22/07231-7 - Plasticity and functional modulation of intrinsically disordered proteins, AP.TEM

Abstract

Protein aggregation plays a crucial role in the pathology of neurodegenerative diseases, particularly Alzheimer's disease, where beta-amyloid (AB) peptides form toxic aggregates. Understanding the mechanisms driving AB aggregation is essential for developing therapeutic interventions. This project aims to investigate the energy landscape associated with AB40 and AB42 aggregation using molecular dynamics simulations and the Energy Landscape Visualization Method (ELViM). ELViM, developed at UNESP, provides a multidimensional approach to analyzing biomolecular conformational spaces without relying on reaction coordinates or predefined structures. By combining computational simulations conducted at National Chung Cheng University (CCU) with ELViM-based analysis, we will identify key conformational states, aggregation pathways, and structural determinants influencing oligomer formation. This collaboration will advance our understanding of intrinsically disordered protein (IDP) aggregation and contribute to the development of new computational methodologies for studying neurodegenerative disease mechanisms. Additionally, this project will strengthen international partnerships, provide training opportunities for students, and lay the groundwork for future funding initiatives focused on IDP-related diseases. (AU)