| Grant number: | 21/15028-4 |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| Start date: | June 01, 2022 |
| End date: | November 30, 2026 |
| Field of knowledge: | Physical Sciences and Mathematics - Physics - Condensed Matter Physics |
| Principal Investigator: | Vitor Barbanti Pereira Leite |
| Grantee: | Murilo Nogueira Sanches |
| 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 |
| Associated research grant: | 22/07231-7 - Plasticity and functional modulation of intrinsically disordered proteins, AP.TEM |
| Associated scholarship(s): | 23/08101-2 - Exploring the energy landscape of amyloid-beta oligomers and akyrin repeat-proteins, BE.EP.DR |
Abstract Folding and functional mechanisms of proteins are fundamental problems inunderstanding biological machinery. Under physiological conditions, proteins are generallycharacterized by native structural conformations. These structures significantly facilitate the investigation of protein functioning, as their structural information serves as order parameters and reaction coordinates of the studied processes and mechanisms. There is, however, an even more challenging class of proteins, which lack well-defined native states, which are known as Intrinsically Disordered Proteins (IDPs). These are characterized bya non-funneled energy landscape with many local minima. Their high conformational flexibility is responsible for high plasticity and functional modulation, making them themain source of protein dysfunctions, such as those associated with degenerative diseases and Cancers. The recent Energy Landscape Visualization Method (ELViM) has been shown to be a potential alternative for the analysis of this class of proteins, since it does not need a specific reaction coordinate to analyze energy surfaces. This project proposes touse this new visualization method to study two processes involving disordered proteins: the aggregation of amyloid-² oligomers and phosphorylations in the N a+/H+ Exchanger isoform 1 (NHE1cdt). While amyloid-² aggregation is linked to the development of Alzheimer's Disease, changes in NHE1cdt can lead to cardiac ischemia and the development of Cancer. In this sense, the study of these proteins is relevant both for understanding the underlying energy landscape of IDPs, as well as for understanding the diseases associated with them. The continuous exploration and parameterization of ELViM is an integralpart of this plan. One of the adjacent objectives in this project is to participate in the development of a web-server for automated use of ELViM. (AU) | |
| News published in Agência FAPESP Newsletter about the scholarship: | |
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