Study of the Potential Energy Landscape of the Transcription Anti-terminator RfaH

• Grant number: 23/06090-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Physics
• Principal Investigator: Vitor Barbanti Pereira Leite
• Grantee: Gustavo de Souza Catanoce
• 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

Abstract

Since the advent of Molecular Biology, the search for fundamental models capable of explaining the relationships among amino acid sequence, protein structure, and protein function has received central attention due to its relevance and impact in various fields of knowledge. Theoretically, the Energy Landscape approach has played a key role in elucidating the protein folding process and function. However, obtaining relevant information about such mechanisms is still challenging due to the complexity of such systems and the large dimensionality of investigated systems through molecular simulations. Thus, simplified models and methodologies capable of reducing the system dimensionality and extracting relevant features have been of great help. The Energy Landscape Visualization Method (ELViM) has been developed by our group to produce an intuitive visualization of the folding funnel, with the potential to detail molecular mechanisms. In this project, we intend to implement a Structure-Based Model (SBM) to simulate and explore the conformational space of the virulence factor RfaH from Escherichia coli. Unlike proteins having a single functional conformation, the C-terminal domain (CTD) of RfaH undergoes a dramatic conformational rearrangement switching from an ±-helix hairpin to a ²-barrel conformation. The application of ELViM to such a system has the potential to generate an intuitive visualization of this multi-funnel surface, unveiling transition states and elucidating the molecular mechanism responsible for the ±-to-² transition.