Exploring the energy landscape of amyloid-beta oligomers and akyrin repeat-proteins

• Grant number: 23/08101-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2023
• End date: September 30, 2024
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Vitor Barbanti Pereira Leite
• Grantee: Murilo Nogueira Sanches
• Supervisor: Peter Wolynes
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
• Institution abroad: Rice University, United States
• Associated to the scholarship: 21/15028-4 - Elucidating the functional plasticity of intrinsically disordered proteins by the study of energy landscape, BP.DR

Abstract

Understanding the processes of protein aggregation, folding, and functional mecha-nisms is a fundamental challenge in the field of biological physics. The energy landscapetheory has emerged as a valuable framework for gaining insights into these complex phenom-ena. In this collaborative project between research groups at CTBP and UNESP, we aim toaddress two key topics utilizing energy landscape theory approaches. The first topic focuseson amyloid-² (A²), an intrinsically disordered protein known to form fibrous aggregatesassociated with Alzheimer's disease. Our objective is to investigate the formation of A²oligomers, which play a crucial role in the development of A² fibers. The second topicof our research involves the folding of repeat proteins. Specifically, we will explore howmutations in an ankyrin repeat protein impact its energy landscape and folding pathways.Through a combination of molecular dynamics simulation and data analysis using theEnergy Landscape Visualization Method, we will delve into these two interconnected topics.We anticipate uncovering valuable insights into the underlying mechanisms driving proteinaggregation and folding. (AU)