Advancing Antibacterial Research with MeluXina: The Role of Small Peptides 

Introduction

Short peptides exert a significant potential in biotechnological, agricultural, and clinical applications due to their membrane-active properties. Many of such peptides are of natural origin like peptaibols that are produced by fungi of the species Trichoderma, however there exist also artificially designed peptides like Chignolin. Small peptides can form ion channels in lipid bilayers, acting as potent antibiotics. Prof. Vangelis Daskalakis and his team at University of Patras, that includes the research associate Mr. Chatzikyriakos Konstantinos, study the configurational space of small peptides and give insight into the sequence – structure – function relationship. The team utilized the MeluXina supercomputer to explore the conformational changes of such small peptides, providing insights for designing new membrane-active biomolecules against bacterial infections and plant pathogens.

The Challenge of This Research

Small peptides present unique challenges in their study:

1. Complex Conformational Dynamics: The bioactivity of peptides is linked to their ability to switch between different helical conformations, a property difficult to capture experimentally.
2. High Computational Demand: Simulating the passive transport of peptides across biological membranes involves timescales beyond the reach of classical Molecular Dynamics (MD).
3. Structural Elucidation: Understanding the structural and dynamic properties of peptides is essential for designing effective antibiotics, but requires advanced computational methods, like Markov State Modeling and Machine Learning.

The MeluXina Solution

To address these challenges, the project employs the computational power of MeluXina:

• Enhanced Sampling Techniques: Using enhanced sampling MD variants to simulate the structural transitions of the peptides. This was made possible only by the availability of many computational resources at the (High-Performance Computing) HPC level.

• High-Performance Computing: Utilizing GROMACS 2021.4 and PLUMED 2.7.3 for efficient simulations on MeluXina’s CPU partition.

• Integration with Experimental Data: Evaluating the computational results with experimental crystallography to validate and refine models. This is only possible with large-scale sampling at the μs time scale.

The Impact

The expected impact of this research includes:

• Antibacterial and Agricultural Applications: Providing a basis for designing bioactive peptides to combat bacterial infections, including antibiotic-resistant superbugs, and enhancing agricultural production by targeting plant pathogens.

• Scientific Advancements: Contributing to the field of computational biochemistry by advancing our understanding of peptide-membrane interactions and the structural dynamics of bioactive peptides.

• Resource Optimization: Demonstrating the feasibility and benefits of using high-performance computing for complex biophysical simulations.

Conclusion

This project represents a significant advancement in the study of membrane-active peptides, utilizing the powerful capabilities of the MeluXina supercomputer. By exploring the bioactivity and structural properties of small peptides, Prof. Daskalakis’s team aims to pave the way for new antibiotic designs and agricultural applications. The outcomes will not only enhance scientific knowledge but also provide practical solutions for pressing global challenges in healthcare and agriculture.