Effects of cosolvents on the folding and function of riboswitches

• Grant number: 23/02071-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: July 01, 2023
• End date: June 30, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Leandro Martinez
• Grantee: Ander Francisco Pereira
• Supervisor: José Nelson Onuchic
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Rice University, United States
• Associated to the scholarship: 20/04549-0 - Solvent effects on protein folding thermodynamics, BP.DR

Abstract

Riboswitches are a type of RNA molecule that act as receptors for specific metabolites and control gene expression. When a metabolite binds to the aptamer domain of the riboswitch, it causes alterations in its secondary and tertiary structure. Riboswitches, like proteins, are also modulated by various external factors, including cosolvents. However, the effects of cosolvents on the stability of RNA and protein molecules can vary due to differences in their composition. In this research project, we aim to comprehend the impact of different solvents (water, amino acid, trimethylamine N-oxide (TMAO), and urea) and Mg2+ on the folding and function of riboswitches. While previous experimental studies have explored the effects of these cosolvents on riboswitches, the underlying molecular mechanisms are still not well understood. To fill this knowledge gap, we will use enhanced sampling molecular dynamics simulations and appropriate analysis tools to shed light on the thermodynamics and kinetics of riboswitches under unusual conditions. (AU)