Biophysical Design of Antimicrobial peptides and Innovative Molecular Descriptors – BioAmpMode

Project participants:

Juraj Simunić, Nada Ilić, Mario Novkovic, Goran Gajski, Frances Separovic, Alessandro Tossi, Anita Kriško, Jelena Sedlar, Damir Vukičević, Bernarda Lovrinčević, Tomislav Došlić, Marija Raguž, Nataša Vučemilović-Alagić, Mara Kozić, Lara Romac, Lucija Krce, Ana Maravić, Luka Gujinović, Tomislav Rončević, Ivana Goić Barišić

Head: Damir Vukičević

University of Split, Faculty of Science

The starting point of this interdisciplinary project is bioinformatic and chemoinformatic data collection connecting molecular structure with physico-chemical and biological properties. In the case of antimicrobial peptides, measured biological activity and therapeutic index data will be collected from published papers with the goal of constructing robust and accurate predictive models. A large amount of data regarding the 20 natural amino acids attributes will also be collected and analysed. We plan to propose new scales of amino-acid attributes that may be a basis for a multitude of future studies. In our experience, construction of good predictive models is not possible without using biophysical insights to propose appropriate molecular descriptors crucial for data-mining procedure and model building. These models should be based on newly developed molecular descriptors. Study of molecular descriptors will be important part of this project, their extremal properties (as indicators of the most active compounds), their complexity of calculation (since exhaustive search for optimal compounds can be computationally demanding) and their interrelationships. Dedicated algorithms for in-silico identification or proposal of structures with the desired properties will be built and verified through synthesis, characterization and testing of predicted antimicrobials. The activity, selectivity, conformation and mechanism of action of lead compounds will be explored using biophysical, biochemical and microbiological techniques. Preliminary investigations by our group of graduate, doctoral and postdoctoral biophysics students has already led to the identification of two designed peptides as being very active against pan-resistant Acetinobacter baumanni, so that initial drug development is within the scope of this project with the aim of finding new classes of non-toxic peptide antibiotics active against multidrug resistant bacteria.