A5085108119- DNA and Nucleic Acid Chemistry
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- SARS-CoV-2 and COVID-19 Research
- Lipid Membrane Structure and Behavior
- ATP Synthase and ATPases Research
- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- Protein Structure and Dynamics
- Force Microscopy Techniques and Applications
- Antibiotic Resistance in Bacteria
- Ion channel regulation and function
- Metal complexes synthesis and properties
- Spectroscopy and Quantum Chemical Studies
- Advanced biosensing and bioanalysis techniques
- Viral gastroenteritis research and epidemiology
- Cell Image Analysis Techniques
- Animal Virus Infections Studies
- Nicotinic Acetylcholine Receptors Study
- Bioinformatics and Genomic Networks
- Mitochondrial Function and Pathology
- Virus-based gene therapy research
- Antimicrobial Peptides and Activities
- Machine Learning in Materials Science
Gdańsk University of Technology
2016-2025
Institute for Research in Biomedicine
2020-2025
Gdańsk Medical University
2023
Medical University of Warsaw
2023
University of Oslo
2023
University of Gdańsk
2014-2023
Institute for Research in Biomedicine
2020-2023
SciencePharma (Poland)
2023
In eukaryotic cells, different organelles interact at membrane contact sites stabilized by tethers. Mitochondrial mitofusin 2 (MFN2) acts as a tether that interacts with an unknown partner on the endoplasmic reticulum (ER). this work, we identified MFN2 splice variant ERMIT2 ER tethering of MFN2. Splicing produced and ERMIN2, two ER-specific variants. ERMIN2 regulated morphology, whereas localized ER-mitochondria interface interacted mitochondrial mitofusins to mitochondria. This allowed...
Poor efficiency of chemotherapeutics in the eradication Cancer Stem Cells (CSCs) has been driving search for more active and specific compounds. In this work, we show how cell density-dependent stage culture profiles can be used drug development workflows to achieve robust activity (IC50 EC50) results. Using flow cytometry light microscopy, characterized cytological HL-60-, A-549-, HEK-293-derived sublines with a focus on their primitive content. We then range cytotoxic substances—C-123,...
We combine molecular dynamics, statistical mechanics, and hybrid quantum mechanics/molecular mechanics simulations to describe mechanistically the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp). Our study analyzes binding mode of both natural triphosphate substrates as well remdesivir (the active form drug), which is bound preferentially over ATP by RdRp while being poorly recognized human II (RNA Pol II). A comparison incorporation rates...
The S:A222V point mutation, within the G clade, was characteristic of 20E (EU1) SARS-CoV-2 variant identified in Spain early summer 2020. This mutation has since reappeared Delta subvariant AY.4.2, raising questions about its specific effect on viral infection. We report combined serological, functional, structural and computational studies characterizing impact this mutation. Our results reveal that promotes an increased RBD opening slightly increases ACE2 binding as compared to parent...
Despite the negative charge of DNA backbone, acidic residues (Asp/Glu) commonly participate in base readout, with a strong preference for cytosine. In fact, solved DNA/protein structures, cytosine is recognized almost exclusively by Asp/Glu through direct hydrogen bond, while at same time, adenine, regardless its amino group, shows no propensity Asp/Glu. Here, we analyzed contribution to sequence-specific binding using classical and ab initio simulations selected transcription factors found...
Amphotericin B is a lifesaving polyene antibiotic used in the treatment of systemic mycoses. Unfortunately, pharmacological applicability this drug limited because its severe toxic side effects. At same time, lack well-defined mechanism selectivity hampers efforts to rationally design safer derivatives. As primarily targets biomembranes both fungi and humans, new insights into binding amphotericin lipid membranes can be helpful unveiling molecular mechanisms underlying activity toxicity. We...
We present a physics-based machine learning approach to predict in vitro transcription factor binding affinities from structural and mechanical DNA properties directly derived atomistic molecular dynamics simulations. The method is able obtained with techniques as different uPBM, gcPBM HT-SELEX an excellent performance, much better than existing algorithms. Due its nature, the can be extended epigenetic variants, mismatches, mutations, or any non-coding nucleobases. When complemented...
Omicron BA.1 is a highly infectious variant of SARS-CoV-2 that carries more than thirty mutations on the spike protein in comparison to Wuhan wild type (WT). Some mutations, located receptor-binding domain (RBD), are exposed surrounding solvent and known help evade immunity. However, impact buried RBD conformations mechanics opening less evident. Here, we use all-atom molecular dynamics (MD) simulations with metadynamics characterize thermodynamic RBD-opening ensemble, identifying...
Abstract Amphotericin B (AmB) is a potent but toxic drug commonly used to treat systemic mycoses. Its efficiency as therapeutic agent depends on its ability discriminate between mammalian and fungal cell membranes. The association of AmB monomers in an aqueous environment plays important role selectivity, oligomers formed prior membrane insertion – presumably dimers are believed act differently (ergosterol-rich) (cholesterol-rich) In this work, we investigate the initial steps...
The voltage gated (Kv) slow-inactivating delayed rectifier channel regulates the development of hollow organs zebrafish. functional consists tetramer electrically active Kcnb1 (Kv2.1) subunits and Kcng4b (Kv6.4) modulatory or silent subunits. two mutations in zebrafish kcng4b gene – kcng4b-C1 kcng4b-C2 (Gasanov et al., 2021) have been studied during ear using electrophysiology, developmental biology silico structural modelling. mutation causes a C-terminal truncation characterized by mild...
Membrane-active antibiotics are known to selectively target certain pathogens based on cell membrane properties, such as fluidity, lipid ordering, and phase behavior. These in turn modulated by the composition of a bilayer particular presence type sterols. Amphotericin B (AmB), golden standard antifungal treatment, exhibits higher activity toward ergosterol-rich fungal membranes, which permits its use against systemic mycoses; however, selectivity for membranes is far from satisfactory...
Osmolytes are a class of small organic molecules that shift the protein folding equilibrium. For this reason, they accumulated by organisms under environmental stress and find applications in biotechnology where proteins need to be stabilized or dissolved. However, despite years research, debate continues over exact mechanisms underpinning stabilizing denaturing effect osmolytes. Here, we simulated mechanical denaturation lysozyme different solvent conditions study molecular mechanism which...
F1-ATPase is a highly efficient molecular motor that can synthesize ATP driven by mechanical torque. Its ability to function reversibly in either direction requires tight mechanochemical coupling between the catalytic domain and rotating central shaft, as well temporal control of substrate binding product release. Despite great efforts significant progress, details this synchronized fine-tuned energy conversion mechanism are not fully understood. Here, we use extensive dynamics simulations...
In this study, we established a dynamic micromodel of urinary tract infection to analyze the impact UT-segment-specific outflow on persistence E. coli colonization. We found that adherence Dr+ bladder T24 transitional cells and type IV collagen is maximal at lowest shear stress reduced by any increase in flow velocity. The analyzed was effective whole spectrum physiological almost irreversible over entire range generated force. Once bound host or collagen, they did not detach even presence...
Abstract Exascale computing has been a dream for ages and is close to becoming reality that will impact how molecular simulations are being performed, as well the quantity quality of information derived them. We review biomolecular field anticipating these new architectures, making emphasis on recent work from groups in BioExcel Center Excellence High Performance Computing. exemplified power simulation strategies with done by HPC community fight Covid‐19 pandemics. This article categorized...
Target search as performed by DNA-binding proteins is a complex process, in which multiple factors contribute to both thermodynamic discrimination of the target sequence from overwhelmingly abundant off-target sites and kinetic acceleration dynamic interrogation. TRF1, protein that binds telomeric tandem repeats, faces an intriguing variant problem where are clustered within short fragments chromosomal DNA. In this study, we use extensive (>0.5 ms total) MD simulations study dynamical...
In this study, the interaction of cisplatin (1) and two potential antitumoral Pt(II) complexes (2 3) with a model DMPC bilayer was investigated by multinuclear NMR spectroscopy MD simulations in order to understand its implication for different properties shown three complexes. particular, (31)P, (13)C (2)H solid state experiments were performed obtain information on phase structure, transitions structural dynamic changes phospholipid upon platinum On other hand, calculations yielded free...
High-quality dynamic visuals are needed at all levels of science communication, from the conference hall to classroom. As scientific journals embrace new article formats, many key concepts-particularly, in structural biology-are also more easily conveyed as videos than still frames. Notwithstanding, design and rendering a complex molecular movie remain an arduous task. Here, we introduce Molywood, robust intuitive tool that builds on capabilities Visual Molecular Dynamics (VMD) automate...
Amphotericin B (AmB), one of the most powerful but also toxic drugs used to treat systemic mycoses, is believed selectively permeabilize fungal cell membranes ions in a sterol-dependent manner.
The functioning of the human eye in extreme range light intensity requires a combination high sensitivity photoreceptors with their photostability. Here, we identify regulatory mechanism based on dynamic modulation absorption by xanthophylls retina, realized reorientation pigment molecules induced trans–cis photoisomerization. We explore this photochemically switchable system using chromatographic analysis coupled microimaging fluorescence lifetime and Raman scattering, showing it at work...