Coarse graining analysis of the interaction of antimicrobial and cell penetrating peptides with lipid vesicles

• Grant number: 19/26557-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: September 22, 2020
• End date: September 21, 2021
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Iolanda Midea Cuccovia
• Grantee: Peter Park
• Supervisor: Siewert Jan Marrink
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Groningen, Netherlands
• Associated to the scholarship: 19/03023-8 - How do cell penetrating peptides enter cells?, BP.DD

Abstract

Cationic membrane-active peptides (CMAP) are protagonists in many processes involving lipid membranes such as pore formation, vesicle fusion and rupture. Two CMAP groups stand out as potential novel drug or drug carrier candidates. Antimicrobial peptides (AMP), are a promising class of antibacterial agents and cell-penetrating peptides (CPP), are already candidates for drug-delivery. Many AMP and CPP have been discovered, had their secondary structure analyzed in model membranes, and tested in vitro. However, their exact molecular mechanism of action is still obscure, which in turn presents an obstacle for the extensive use of CMAP. Molecular Dynamics simulations can give us relevant atomistic detailed information and have been used for many peptide/membrane systems, albeit at low peptide/lipid ratios.Here we propose a computational study of TAT and BP100 on vesicles at increasing peptide concentrations using a coarse-grained model. The information obtained by MD simulations will provide crucial pieces of information on the peptide aggregation, vesicle shape and outcome of peptide/lipid systems, which can be directly compared to experimental results with model membranes, allowing the detailed description of AMP and CPP action on membranes. (AU)