Probing the mechanism of action of peptides with antimicrobial and anticancer potential on cell membranes

• Grant number: 25/05278-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2025
• End date: January 31, 2029
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Vitor Barbanti Pereira Leite
• Grantee: Juliana Bueno de Camargo
• 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
• Associated research grant: 22/07231-7 - Plasticity and functional modulation of intrinsically disordered proteins, AP.TEM

Abstract

The indiscriminate use of antibiotics has been selecting bacterial strains resistant to abroad spectrum of this type of drug. Thus, the development of new antibiotics that act throughpathways that have not yet been explored and, mainly, which are difficult to adapt to bacteria, is ofgreat interest. Polybia-MP-I (MP-I, or simply MP1) is an antimicrobial peptide (AMP) extractedfrom the venom of a social wasp from Brazil, Polybia paulista. MP1, cationic at physiological pH,acts on the bacterial cell membrane, consisting of zwitterionic and anionic phospholipids, inducingcell lysis. Also, recent studies have indicated that the anticancer action of MP1 may be associatedwith the fact that tumor cells have an excess of anionic phospholipids on their surface. The detailsof MP1's mechanism of action on bacterial and cancer cells are still not completely clear. In thisproject, we propose to study the process of adsorption and action of MP1 and some syntheticanalogues on lipid bilayers, used as a model of bacterial and carcinogenic cell membranes, throughsimulations of Molecular Dynamics (MD) at equilibrium and at constant pH (CpHMD). Withthese trajectories, the structural properties regarding the peptide's folding and energy landscapecan be inferred, as well as changes at the lipid bilayer caused by the peptide's adsorption. Theunderstanding of these peptide mechanisms at the atomic/molecular level will help to rationallyexplore the antibacterial and chemotherapeutic potential of MP1. Furthermore, the know-how forMP1 can be used to propose more efficient and selective synthetic molecules. In the same researchand methodology topic, another system will also be studied which is a fragment of the retinolisomerase RPE65; it plays a fundamental role in the functional cycle of the retina.