Open science is now established as an important paradigm for publicly funded research. The main principle being that to ensure best use of research data and integrity of the scientific process the information from experiments should be made widely and freely available. However, dedicated technical infrastructure to enable useful access to comprehensive experimental information in molecular biophysics is lacking, in particular in regard to repositories for raw measurement data. The Molecular Biophysics Database (MBDB) was created to fill this gap. The MBDB provides a common and extensible framework to store and access raw measurement data from a growing number of biophysical methods, currently including bio-layer interferometry, isothermal titration calorimetry, surface plasmon resonance, and microscale thermophoresis, with additional methods planned for the future. Alongside the raw measurement data from these methods, a rich set of metadata to enable data reuse is captured in accordance with the FAIR data management principles. An overview of the data models and technologies that were used to create the MBDB is presented here.

• Klíčová slova
• Database, FAIR principles, Metadata model, Molecular biophysics, Raw data, Repository,
• Publikační typ
• časopisecké články MeSH

Biophysics is an interdisciplinary science that applies the theories and methods of physics to understand biological systems. It encompasses a wide range of topics, from the molecular mechanisms within cells to the physical properties of organisms and ecosystems. The goal of biophysics is to uncover the physical principles underlying the structure and function of biological molecules, cells, and cellular systems, providing a deeper understanding of life itself. The Institute of Biophysics, Czech Academy of Sciences (IBP) stands as a beacon of excellence in the field of biophysical research in the Czech Republic. This article delves into its history, structure, research areas, and major scientific achievements, highlighting the role of IBP in the global scientific community.

• Klíčová slova
• Biophysical methods, Biophysics, DNA damage repair, Ionizing radiation, Radiotherapy,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

This review focuses on the influence of oxidized phosphatidylcholines (oxPCs) on the biophysical properties of model membranes and is limited to fluorescence, EPR, and MD studies. OxPCs are divided into two classes: A) hydroxy- or hydroperoxy-dieonyl phospatidylcholines, B) phospatidylcholines with oxidized and truncated chains with either aldehyde or carboxylic group. It was shown that the presence of the investigated oxPCs in phospholipid model membranes may have the following consequences: 1) decrease of the lipid order, 2) lowering of phase transition temperatures, 3) lateral expansion and thinning of the bilayer, 4) alterations of bilayer hydration profiles, 5) increased lipid mobility, 6) augmented flip-flop, 7) influence on the lateral phase organisation, and 8) promotion of water defects and, under extreme conditions (i.e. high concentrations of class B oxPCs), disintegration of the bilayer. The effects of class A oxPCs appear to be more moderate than those observed or predicted for class B. Many of the abovementioned findings are related to the ability of the oxidized chains of certain oxPCs to reorient toward the water phase. Some of the effects appear to be moderated by the presence of cholesterol. Although those biophysical alternations are found at oxPC concentrations higher than the total oxPC concentrations found under physiological conditions, certain organelles may reach such elevated oxPC concentrations locally. It is a challenge for the future to correlate the biophysics of oxidized phospholipids to metabolic studies in order to define the significance of the findings presented herein for pathophysiology. This article is part of a Special Issue entitled: Oxidized phospholipids-their properties and interactions with proteins.

• MeSH
• biofyzikální jevy * MeSH
• elektronová paramagnetická rezonance MeSH
• fluorescence MeSH
• fosfolipidy chemie   metabolismus   MeSH
• lidé MeSH
• lipidové dvojvrstvy chemie   metabolismus   MeSH
• oxidace-redukce MeSH
• simulace molekulární dynamiky * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• fosfolipidy MeSH
• lipidové dvojvrstvy MeSH

This paper has been prepared to commemorate the 70th anniversary of the Institute of Biophysics of the Czech Academy of Sciences (IBP CAS), which has a long-standing tradition in researching the biological effects of ionizing radiation (IR). Radiobiology has recently gained renewed importance due to several compelling factors. The demand for a better understanding of the biological effects of both low and high doses of various types of ionizing radiation, along with improved radiation protection, is increasing-particularly in the context of critical ongoing human activities such as medical diagnostics, radiotherapy, and the operation of nuclear power plants. This demand also extends to newly emerging scenarios, including the development of hadron and FLASH radiotherapy, as well as mixed radiation field exposures related to planned manned missions to Mars. Unfortunately, there is also an urgent need to address the heightened risk of nuclear materials and weapons misuse by terrorists or even rogue states. Additionally, nuclear energy is currently the only viable alternative that can provide efficient, sustainable, and ecological coverage for the dramatically increasing current and future energy demands. Understanding the risks of IR exposure necessitates exploring how different types of IR interact with living organisms at the most fundamental level of complexity, specifically at the level of molecules and their complexes. The rising interest in radiobiology is, therefore, also driven by new experimental opportunities that enable research at previously unimaginable levels of detail and complexity. In this manuscript, we will address the important questions in radiobiology, focusing specifically on the mechanisms of radiation-induced DNA damage and repair within the context of chromatin architecture. We will emphasize the differing effects of photon and high-LET particle radiation on chromatin and DNA. Both forms of IR are encountered on Earth but are particularly significant in space.

• Klíčová slova
• Biological effects of ionizing radiation, Chromatin architecture at micro- and nano-scale, DNA damage and repair, Densely ionizing (high-LET) particle radiation, Institute of biophysics of the Czech academy of sciences, Microscopy, Photon radiation, Radiobiological research, Single molecule localization microscopy (SMLM),
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• Klíčová slova
• caveolae, cell membrane, fluorescence microscopy, membrane properties, membrane trafficking, nanodomains, superresolution microscopy, tetraspanins,
• Publikační typ
• úvodníky MeSH

The ability of the four-stranded guanine (G)-DNA motif to incorporate nonstandard guanine analogue bases 6-oxopurine (inosine, I), 6-thioguanine (tG), and 6-thiopurine (tI) has been investigated using large-scale molecular dynamics simulations. The simulations suggest that a G-DNA stem can incorporate inosines without any marked effect on its structure and dynamics. The all-inosine quadruplex stem d(IIII)(4) shows identical dynamical properties as d(GGGG)(4) on the nanosecond time scale, with both molecular assemblies being stabilized by monovalent cations residing in the channel of the stem. However, simulations carried out in the absence of these cations show dramatic differences in the behavior of d(GGGG)(4) and d(IIII)(4). Whereas vacant d(GGGG)(4) shows large fluctuations but does not disintegrate, vacant d(IIII)(4) is completely disrupted within the first nanosecond. This is a consequence of the lack of the H-bonds involving the N2 amino group that is not present in inosine. This indicates that formation of the inosine quadruplex could involve entirely different intermediate structures than formation of the guanosine quadruplex, and early association of cations in this process appears to be inevitable. In the simulations, the incorporation of 6-thioguanine and 6-thiopurine sharply destabilizes four-stranded G-DNA structures, in close agreement with experimental data. The main reason is the size of the thiogroup leading to considerable steric conflicts and expelling the cations out of the channel of the quadruplex stem. The G-DNA stem can accommodate a single thioguanine base with minor perturbations. Incorporation of a thioguanine quartet layer is associated with a large destabilization of the G-DNA stem whereas the all-thioguanine quadruplex immediately collapses.

• MeSH
• biofyzika MeSH
• biofyzikální jevy MeSH
• DNA chemie   MeSH
• inosin chemie   MeSH
• iontové kanály chemie   MeSH
• konformace nukleové kyseliny * MeSH
• merkaptopurin chemie   MeSH
• molekulární modely MeSH
• sodík chemie   MeSH
• termodynamika MeSH
• thioguanin chemie   MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA MeSH
• inosin MeSH
• iontové kanály MeSH
• merkaptopurin MeSH
• sodík MeSH
• thioguanin MeSH

• MeSH
• biofyzika MeSH
• biofyzikální jevy MeSH
• DNA chemie   MeSH
• fosfáty chemie   MeSH
• konformace nukleové kyseliny MeSH
• nukleové kyseliny chemie   MeSH
• oligodeoxyribonukleotidy chemie   MeSH
• oligonukleotidy chemie   MeSH
• organofosfonáty chemie   MeSH
• sekvence nukleotidů MeSH
• termodynamika MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA MeSH
• fosfáty MeSH
• nukleové kyseliny MeSH
• oligodeoxyribonukleotidy MeSH
• oligonukleotidy MeSH
• organofosfonáty MeSH

Variegate porphyria is caused by mutations in the protoporphyrinogen oxidase IX (PPOX, EC 1.3.3.4) gene, resulting in reduced overall enzymatic activity of PPOX in human tissues. Recently, we have identified the His333Arg mutation in the PPOX protein (PPOX(H333R)) as a putative founder mutation in the Moroccan Jewish population. Herein we report the molecular characterization of PPOX(H333R) in vitro and in cells. Purified recombinant PPOX(H333R) did not show any appreciable enzymatic activity in vitro, corroborating the clinical findings. Biophysical experiments and molecular modeling revealed that PPOX(H333R) is not folded properly and fails to adopt its native functional three-dimensional conformation due to steric clashes in the vicinity of the active site of the enzyme. On the other hand, PPOX(H333R) subcellular distribution, as evaluated by live-cell confocal microscopy, is unimpaired suggesting that the functional three-dimensional fold is not required for efficient transport of the polypeptide chain into mitochondria. Overall, the data presented here provide molecular underpinnings of the pathogenicity of PPOX(H333R) and might serve as a blueprint for deciphering whether a given PPOX variant represents a disease-causing mutation.

• Klíčová slova
• Heme synthesis, Protoporphyrinogen oxidase IX, Variegate porphyria,
• MeSH
• biofyzikální jevy MeSH
• buněčné linie MeSH
• flavoproteiny chemie   genetika   izolace a purifikace   MeSH
• kinetika MeSH
• lidé MeSH
• mitochondriální proteiny chemie   genetika   izolace a purifikace   MeSH
• molekulární modely MeSH
• multimerizace proteinu MeSH
• mutace genetika   MeSH
• protoporfyrinogenoxidasa chemie   genetika   izolace a purifikace   MeSH
• sekvence aminokyselin MeSH
• stabilita enzymů MeSH
• subcelulární frakce metabolismus   MeSH
• teplota MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• flavoproteiny MeSH
• mitochondriální proteiny MeSH
• PPOX protein, human MeSH Prohlížeč
• protoporfyrinogenoxidasa MeSH

MOTIVATION: Metallothionein-III (MT-III) displays neuro-inhibitory activity and is involved in the repair of neuronal damage. An altered expression level of MT-III suggests that it could be a mitigating factor in Alzheimer's disease (AD) neuronal dysfunction. Currently there are limited marketed drugs available against MT-III. The inhibitors are mostly pseudo-peptide based with limited ADMET. In our present study, available database InterBioScreen (natural compounds) was screened out for MT-III. Pharmacodynamics and pharmacokinetic studies were performed. Molecular docking and simulations of top hit molecules were performed to study complex stability. RESULTS: Study reveals potent selective molecules that interact and form hydrogen bonds with amino acids Ser-6 and Lys-22 are common to established melatonin inhibitors for MT-III. These include DMHMIO, MCA B and s27533 derivatives. The ADMET profiling was better with comparable interaction energy values. It includes properties like blood brain barrier, hepatotoxicity, druggability, mutagenicity and carcinogenicity. Molecular dynamics studies were performed to validate our findings.

• Klíčová slova
• ADMET, Alzheimer’s disease, Metallothionein-III, Molecular dynamics, Virtual screening,
• MeSH
• Alzheimerova nemoc metabolismus   patologie   MeSH
• biofyzikální jevy MeSH
• lidé MeSH
• metalothionein 3 MeSH
• proteiny nervové tkáně antagonisté a inhibitory   chemie   MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• metalothionein 3 MeSH
• proteiny nervové tkáně MeSH

Human immunity involves both innate and adaptive defence mechanisms, with inflammation playing a central role in responding to cellular injury, pathogenic infections, and allergic stimuli. Reactive oxygen species (ROS) are closely associated with the onset and progression of inflammation. While moderate ROS levels function as crucial signalling molecules, excessive ROS can damage cellular components. This study aimed to evaluate the anti-inflammatory and antioxidant potential of plant-derived bioactive compounds including chlorogenic acid, oleuropein, tomatine, and tyrosol using human monocytic cell models (U-937 and THP-1). Differentiation of U-937 and THP-1 cells was induced prior to treatment with the selected bioactive compounds. Cell morphology and integrity were examined utilizing confocal microscopy. Gene expression stability was evaluated using reference genes β-actin and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Protein expression levels of key inflammatory markers were determined by Western blot analysis. In addition, molecular docking studies were conducted to assess the binding affinity of the compounds to human target proteins [Interleukin-4 (IL-4), 5-Lipoxygenase (LOX-5), Myeloperoxidase (MPO), and Tumor necrosis factor-alpha ( TNF-α)]. No cytotoxic effects were observed in treated cells, and GAPDH was confirmed as a stable reference gene under all experimental conditions. In U-937 cells, treatment with the bioactive compounds led to increased expression of the anti-inflammatory cytokine IL-4 and decreased expression of MPO. Notably, exposure to chlorogenic acid and tyrosol reduced MPO activity. Oleuropein and tyrosol demonstrated a strong suppressive effect on the expression of LOX-5, an enzyme responsible for leukotriene production. All tested bioactive compounds significantly reduced the phorbol 12-myristate 13-acetate (PMA) induced increase in LOX-5 activity. Molecular docking supported the potential of these compounds to interact with key inflammatory proteins, contributing to reduced oxidative stress. The plant-derived compounds, particularly oleuropein and tyrosol from olives, exhibit promising anti-inflammatory and antioxidant effects by modulating ROS-associated signalling pathways and downregulating inflammatory markers. These findings support the therapeutic potential of agricultural waste-derived bioactive in inflammation management and oxidative stress regulation.

• Klíčová slova
• Antioxidants, Bioactive compound, Free radicals, Inflammation, Interleukin-4, LOX-5, Macrophages, Monocytes, Reactive oxygen species,
• MeSH
• antiflogistika * farmakologie   chemie   MeSH
• antioxidancia farmakologie   MeSH
• arachidonát-5-lipoxygenasa metabolismus   MeSH
• fenethylalkohol analogy a deriváty   farmakologie   MeSH
• iridoidní glukosidy farmakologie   MeSH
• iridoidy farmakologie   MeSH
• kyselina chlorogenová farmakologie   MeSH
• lidé MeSH
• makrofágy * účinky léků   metabolismus   MeSH
• monocyty * účinky léků   metabolismus   MeSH
• oxidační stres * účinky léků   MeSH
• peroxidasa metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• simulace molekulového dockingu MeSH
• THP-1 buňky MeSH
• TNF-alfa metabolismus   MeSH
• U937 buňky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 4-hydroxyphenylethanol MeSH Prohlížeč
• antiflogistika * MeSH
• antioxidancia MeSH
• arachidonát-5-lipoxygenasa MeSH
• fenethylalkohol MeSH
• iridoidní glukosidy MeSH
• iridoidy MeSH
• kyselina chlorogenová MeSH
• oleuropein MeSH Prohlížeč
• peroxidasa MeSH
• reaktivní formy kyslíku MeSH
• TNF-alfa MeSH