In silico and physico-chemical characterization of cluster formation dynamics in peptide solutions.

Although antimicrobial peptides are considered one of the most promising alternatives to conventional antibiotics given the alarming increase in bacterial multidrug resistance, many aspects of their mechanism of action remain unclear, in particular the emergence and role of collective phenomena such as the spontaneous formation of nano-sized unstructured objects (clusters) and their effects on the biodynamics. We study this process using two novel peptides from the mucus of the garden snail as an example to reveal its dynamics and bioactivity implications through coordinated in silico and in vitro techniques - molecular dynamics simulations, UV-Vis and fluorescence spectroscopy, and antibacterial activity tests against two representative bacterial strains - one gram-negative ( 3458) and one gram-positive (). The results obtained confirm the impact of the aggregation processes of the peptides on their biological activity and provide insight into possible synergies in their action.

Interferon- as a Potential Inhibitor of SARS-CoV-2 ORF6 Accessory Protein.

The ORF6 protein of the SARS-CoV-2 virus plays a crucial role in blocking the innate immune response of the infected cells by inhibiting interferon pathways. Additionally, it binds to and immobilises the RAE1 protein on the cytoplasmic membranes, thereby blocking mRNA transport from the nucleus to the cytoplasm. In all these cases, the host cell proteins are tethered by the flexible C-terminus of ORF6.

Heparan Sulfate Facilitates Binding of hIFN to Its Cell-Surface Receptor hIFNGR1.

Human interferon-gamma (hIFNγ) is a crucial signaling molecule with an important role in the initialization and development of the immune response of the host. However, its aberrant activity is also associated with the progression of a multitude of autoimmune and other diseases, which determines the need for effective inhibitors of its activity. The development of such treatments requires proper understanding of the interaction of hIFNγ to its cell-surface receptor hIFNGR1.

Availability of technology for managing cancer patients in the Southeast European (SEE) region.

Background: The Southeast European (SEE) region of 10 countries and about 43 million people differs from Western Europe in that most SEE countries lack active cancer registries and have fewer diagnostic imaging devices and radiotherapy (RT) units. The main objective of this research is to initiate a common platform for gathering SEE regional cancer data from the ground up to help these countries develop common cancer management strategies.

Methods: To obtain detailed on-the-ground information, we developed separate questionnaires for two SEE groups: a) ONCO - oncologists regarding cancer treatment modalities and the availability of diagnostic imaging and radiotherapy equipment; and b) REG - national radiation protection and safety regulatory bodies regarding diagnostic imaging and radiotherapy equipment in SEE facilities.

Molecular Mechanism of the Anti-Inflammatory Action of Heparin.

Our objective is to reveal the molecular mechanism of the anti-inflammatory action of low-molecular-weight heparin (LMWH) based on its influence on the activity of two key cytokines, IFNγ and IL-6. The mechanism of heparin binding to IFNγ and IL-6 and the resulting inhibition of their activity were studied by means of extensive molecular-dynamics simulations. The effect of LMWH on IFNγ signalling inside stimulated WISH cells was investigated by measuring its antiproliferative activity and the translocation of phosphorylated STAT1 in the nucleus.

Self-Association of Antimicrobial Peptides: A Molecular Dynamics Simulation Study on Bombinin.

Antimicrobial peptides (AMPs) are a diverse group of membrane-active peptides which play a crucial role as mediators of the primary host defense against microbial invasion. Many AMPs are found to be fully or partially disordered in solution and to acquire secondary structure upon interaction with a lipid membrane. Here, we report molecular dynamics simulations studies on the solution behaviour of a specific AMP, bombinin H2.

Molecular modeling of the effects of glycosylation on the structure and dynamics of human interferon-gamma.

Natural hIFNγ is a glycoprotein with two N-glycosylation sites in each monomer chain, which are independently and differentially glycosylated. Although glycosylation is not necessary for the activity of the cytokine, it was proposed that it protects the cytokine from proteolytic degradation and thus extends its circulatory half-life. Here, we report the development of model structures of glycosylated full-length native hIFNγ homodimers.

His-FLAG Tag as a Fusion Partner of Glycosylated Human Interferon-Gamma and Its Mutant: Gain or Loss?

In order to obtain glycosylated human interferon-gamma (hIFN) and its highly prone to aggregation mutant K88Q, a secretory expression in insect cells was employed. To facilitate recombinant proteins purification, detection, and stability the baculovirus expression vectors were constructed to bear N-terminal His-FLAG tag. Although the obtained proteins were glycosylated, we found that their biological activity was 100 times lower than expected.