Understanding functional mechanisms of proteins and RNAs through energy landscapes

• Grant number: 23/02219-1
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2023
• End date: September 30, 2025
• Field of knowledge: Physical Sciences and Mathematics - Physics
• Principal Investigator: Vitor Barbanti Pereira Leite
• Grantee: Vitor Barbanti Pereira Leite
• 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 researchers: Alexandre Suman de Araujo ; Ingrid Bernardes Santana Martins ; Jorge Chahine ; José Nelson Onuchic ; Rafael Giordano Viegas ; Ronaldo Júnio de Oliveira

Abstract

The energy landscape approach has contributed significantly to the understanding of complex molecular systems, such as the problem of protein folding. This project will focus on the study of energy landscapes of proteins and RNAs using coarse-grained models and statistical physics approaches. The central idea is related to the visualization of the energy surface using the Energy Landscape Visualization Method (ELViM), which is a method developed by our group at IBILCE-UNESP. The ELViM was designed for visualization of the protein folding funnel and has great potential for detailing molecular mechanisms by going beyond the unidimensional representation. We will apply this methodology to complex and challenging biomolecular systems. The topics to be addressed in this project are: (i) Study of energy landscape of proteins with no defined native structure, which are intrinsically disordered proteins (IDPs); (ii) Proteins with singular folding, such as fold-switching, which have more than one native structure, and repeat proteins that present hierarchical folding; (iii) Studies of riboswitch and RNA fragments; (iv) Study of the mechanism of action of peptides on membranes with antimicrobial and anticancer potential. In addition to advancing the understanding of these complex biomolecules, this project also aims to make ELViM widely available as a server on the internet. (AU)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VIEGAS, RAFAEL GIORDANO; MARTINS, INGRID B. S.; SANCHES, MURILO NOGUEIRA; OLIVEIRA, ANTONIO B.; CAMARGO, JULIANA B. DE; PAULOVICH, FERNANDO V.; LEITE, VITOR B. P.. ELViM: Exploring Biomolecular Energy Landscapes through Multidimensional Visualization. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 64, n. 8, p. 8-pg., 2024-03-20. (23/02219-1, 22/08738-8, 23/08101-2, 21/15028-4)

DIAS, RAPHAEL V. R.; PEDRO, RENAN P.; SANCHES, MURILO N.; MOREIRA, GIOVANA C.; LEITE, VITOR B. P.; CARUSO, ICARO P.; DE MELO, FERNANDO A.; DE OLIVEIRA, LEANDRO C.. Unveiling Metastable Ensembles of GRB2 and the Relevance of Interdomain Communication during Folding. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 63, n. 20, p. 10-pg., 2023-10-12. (19/24974-0, 14/17630-0, 21/15028-4, 19/22540-3, 23/02219-1, 16/08753-6)

VIEGAS, RAFAEL G.; MARTINS, INGRID B. S.; LEITE, VITOR B. P.. Understanding the Energy Landscape of Intrinsically Disordered Protein Ensembles. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 64, n. 10, p. 9-pg., 2024-05-07. (23/02219-1, 22/07231-7)

DE OLIVEIRA, VINICIUS M.; MALOSPIRITO, CAIQUE C.; DA SILVA, FERNANDO B.; VIDEIRA, NATALIA B.; DIAS, MARIELI M. G.; SANCHES, MURILO N.; LEITE, VITOR B. P.; FIGUEIRA, ANA CAROLINA M.. Exploring the molecular pathways of the activation process in PPARγ recurrent bladder cancer mutants. Journal of Chemical Physics, v. 161, n. 16, p. 10-pg., 2024-10-28. (23/02219-1, 19/14465-1, 16/02348-2, 18/11614-3, 20/08366-8, 21/15028-4, 19/22540-3, 19/10274-7, 22/07231-7, 16/19766-1)

VIEGAS, RAFAEL G.; SANCHES, MURILO N.; CHEN, ALAN A. A.; PAULOVICH, FERNANDO V.; GARCIA, ANGEL E.; LEITE, VITOR B. P.. Characterizing the Folding Transition-State Ensembles in the Energy Landscape of an RNA Tetraloop. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 63, n. 17, p. 9-pg., 2023-08-22. (21/15028-4, 19/22540-3, 23/02219-1)

DA SILVA, FERNANDO BRUNO; SIMIEN, JENNIFER M.; VIEGAS, RAFAEL G.; HAGLUND, ELLINOR; LEITE, VITOR BARBANTI PEREIRA. Exploring the folding landscape of leptin: Insights into threading pathways. Journal of Structural Biology, v. 216, n. 1, p. 7-pg., 2023-12-14. (23/02219-1)

MARTINS, INGRID B. S.; VIEGAS, RAFAEL G.; SANCHES, MURILO N.; DE ARAUJO, ALEXANDRE S.; LEITE, VITOR B. P.. Probing Mastoparan-like Antimicrobial Peptides Interaction with Model Membrane Through Energy Landscape Analysis. Journal of Physical Chemistry B, v. 128, n. 1, p. 9-pg., 2023-12-30. (22/00347-0, 23/02219-1, 21/15028-4)