HRZZ IP-2022-10-8432 “Investigating the role of association in bioactivity of antimicrobial peptides: from measurements, modeling to design and back” 

Antimicrobial peptides (AMPs) are critical components of almost all forms of life’s innate defence systems, serving as a first line of defence against invading pathogens in plants and animals. As a result, they are being extensively researched, with a focus on their potential as novel anti-infective drug leads, particularly in the context of emerging drug resistance in bacteria, which is one of the great challenges of our time. Starting with designed or naturally occurring AMPs, the proposed study will advance understanding of the structure-function relationship and identify AMPs with potential for clinical application by combining structural and dynamic properties obtained through molecular dynamics simulation with the biological and biophysical characterization of these peptides in the presence of model membranes and measurements of their activity on real membranes in microbial or host cells. The project also aims to create a new program for designing and characterising AMPs using a neural network approach. The main line of research will be to discover the mode of action related to peptide self-assembly behind the observed activity and toxicity. This work will provide opportunities to strengthen the connection between theoretical and experimental work in Split, put into use some of the new equipment acquired in the recent infrastructure project, and establish further cooperation with international laboratories. The project will also advance the quality of research in Split, bringing new research interests and new methodology.

Project workflow

First year of the project

Final meeting – December 13th 2024

• S. Pacor gave a presentation on the results of cytotoxicity assay and flow cytometry of TSO8 fragments.
• Attended: L. Zoranić, T. Rončević, M. Maleš, A. Begić, M. Cvitković, A. Tossi, S. Pacor and A. Caporale

Project initial meeting – March 19th 2024

• A. Begić gave a presentation on the results of molecular dynamics simulations of TSO8 fragments.
• Attended: L. Zoranić, T. Rončević, M. Maleš, A. Begić, A. Tossi, S. Pacor and A. Caporale