Biomolecular Self-Assembly

Founded in 08/2015, the group is focused on biologically relevant molecules and macromolecular complexes, where intermoleculer interactions play a pivotal role in manifesting biological function. We are particularly interested in molecular level understanding of structure, function and mechanisms of membrane active compounds. Our aim is to study and design natural and nature-mimicking species which can be further developed in biomedical applications targeting organism-specific membranes.

Research interests

Membrane targeting peptidic assemblies

The group focuses its research activities on molecular level understanding of structure, function and mechanisms of membrane active compounds, primarily natural and non-natural peptides with antimicrobial potency.
Natural antimicrobial peptides or host defence peptides constitute a part of the innate immune system of the host organisms and help in the fight against invading pathogens. They have a broad-spectrum activity against various bacteria, and fungi, in addition, they also show antiviral and anticancer properties. Their mechanism of action involves disruption of target cell membranes, moreover, they can elicit immunoregulatory actions as well. They represent a promising novel tool to combat multidrug-resistant bacteria, the emerging number of which represents a global threat. Beyond their applicability in human health care, antimicrobial peptides have potential in various fields, e.g. as biopesticide components to protect cultured plants in agriculture, nutrient additives in livestock, food preservatives in food industry, or even in wastewater treatment.

Despite the many advantages of natural antimicrobial peptides over common antibiotics, their proteolytic sensitivity can limit their medical use. In this regard, peptidomimetic agents called foldamers with structural and folding properties comparable to their natural templates can represent a good alternative. Non-natural peptides display excellent self-organising properties ranging from toxic amyloid oligomers to ion channel formation, with tunable applications ranging from tissue engineering through antiviral and antibacterial therapeutics to supramolecular polymer tubes.

Selected related publications:

Molecular engineering of extracellular vesicles

We also focus on standardized isolation and characterization protocol development for extracellular vesicles and on the molecular engineering of these species.
Extracellular vesicles (EVs) are biological nanoparticles, surrounded by a phospholipid bilayer and released by various cells into the extracellular space. They are classified based on their cellular origin, biogenesis and physicochemical properties. They can carry different type of biomolecules (such as DNA, RNA, proteins, phospholipids) which are characteristic to the particular cells producing them. Besides membrane inserted proteins, in vivo systems can also contain biomolecules adsorbed on their surface, known as protein corona. Evs are important mediators of intracellular communication and are involved in many physiological and pathological processes, so they may provide a wealth of information for early diagnosis and treatment of various diseases. Beyond these roles, they can be used as potential delivery vehicles for different drugs, food nutrient, inorganic nanoparticles etc. Therefore, the composition, modulation and characterization of protein corona is essential, as can influence their bioavailability, bio-distribution and their applicability.

Selected publications:

Computational membrane biology

Besides experimental investigations, we employ all-atom Molecular Dynamics (MD), Coarse-Grained MD as well as quantum chemical simulations with numerous antimicrobial peptides (AMP) in order to investigate their behaviour and binding conformations on complex membranes, extracellular vesicles (EVs), and single composition lipid bilayers. We are particularly interested in studiyng peptide interactions with small molecules (eg. with drug molecules, food colors, bacterial and human signalling compounds, etc.). Here it is crucial to understand how how these interactions can cause structural changes in AMPs as well as affect their membrane binding properties. Our studies are often supplemented with molecular Docking tools that helps identifying initial docking sites of the molecules on larger species and assists model building when experimental structural details are lacking. Furthermore simulations enable calculation of electrostatic potentials, entropy, binding free energy and other quantifiable parameters, which greatly helps for objective comparison of different systems. Lastly quantum chemical calculations are also frequenatly used in order to parametrize molecules for MD simulations and also to assess their photophysical and conformational properties.