Search for molecular determinants that govern the process of adsorption of antimicrobial peptides MP-1 and HMP-1 to model membranes for bacterial and cancer cells through the calculation of free energy profiles using Molecular Dynamics

• Grant number: 23/09944-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: December 31, 2024
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Alexandre Suman de Araujo
• Grantee: Cristofer Alan Navarro Gomes
• 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

The indiscriminate use of antibiotics has been selecting bacterial strains resistant to a wide spectrum of this drug. Thus, the development of new drugs that act through antibiotic pathways that have not yet been explored and, mainly, which are difficult to promote bacteria adaptation, is of great interest today. Antimicrobial peptides (AMPs) are small protein particles produced by the immune system of some animals and plants which have action, in addition to being bactericidal, against viruses, fungi, and cancer cells. PAMs, which are cationic at physiological pH, act on the bacterial cell membrane, which is made up of a fraction of anionic phospholipids, inducing pores and leakage of cell contents (cell lysis). Mutations that result in changes in the composition of the cell membrane are rare or unfeasible, indicating that the antibiotic pathway of AMPs has great potential for exploitation. The vertiginous growth in computational power observed in recent decades has allowed the application of computational simulation techniques to complex biological systems. Among the myriad of existing computational simulation methods, the most used currently for studying systems containing biological macromolecules is Molecular Dynamics (MD) and its variants. This method provides accurate and reliable results, in addition to satisfactorily sampling the enormous set of conformations that biomolecules can assume. In the present project, we propose to investigate the molecular determinants that govern the process of adsorption of peptides MP-1 and HMP-1 to mixed lipid bilayers that mimic the cell membrane of bacteria and cancer cells, by calculating free energy profiles using Molecular Dynamics simulations.