Exploring the Barnase Folding Energy Landscape

• Grant number: 25/28189-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2026
• End date: December 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Physics
• Principal Investigator: Vitor Barbanti Pereira Leite
• Grantee: Leonardo da Silva Batista
• 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

This project investigates the folding energy landscape of the barnase protein, a model system widely used in protein physical chemistry due to its well-characterized topology and the presence of relevant intermediate states in the folding mechanism. Barnase exhibits reversible folding and metastable intermediates, making it an appropriate system for validation of computational models.The study will be conducted through computational simulations using structure-based coarse-grained C-alpha models, which allow the folding process to be described with low computational cost while maintaining good agreement with experimental data. The wild-type protein and the I88V and Y17G mutations will be analyzed to assess the effects of point mutations on the energy landscape and folding pathways.Thermodynamic characterization will be performed using the Weighted Histogram Analysis Method (WHAM), while the Energy Landscape Visualization Method (ELViM) will be employed to explore the energy landscape in a multidimensional framework. This approach enables the identification of intermediate states and transition ensembles. The expected outcomes include advancing the understanding of fundamental principles governing protein folding and providing training in computational modeling applied to biological physics. (AU)