Kinase Inhibition via AI-Designed Proteins: A Novel Antibacterial Approach

• Grant number: 25/07922-8
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2026
• End date: January 31, 2029
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Alessandro Silva Nascimento
• Grantee: Alessandro Silva Nascimento
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• City of the host institution: São Carlos

Abstract

This research proposal aims to address the growing threat of antibiotic resistance by developing a novel therapeutic strategy targeting thiamine metabolism in bacterial pathogens. The central focus is on inhibiting the enzyme thiamine monophosphate kinase (ThiL), essential for thiamine pyrophosphate (TPP) biosynthesis in Gram-negative bacteria. Preliminary studies have demonstrated that ThiL is a valid antibacterial target, and its inactivation can disrupt bacterial growth and virulence. The project proposes an innovative approach using AI-driven protein design to generate inhibitory proteins that disrupt ThiL dimerization, thus blocking its activity. The designed proteins will be experimentally validated through interaction assays, biochemical assays, and structural determination. If successful, this research will provide a foundation for developing novel antibacterial therapies and establish a platform for protein engineering focused on therapeutic applications. (AU)