The advent of cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), coupled with computational modeling, has enabled the creation of integrative 3D models of viruses, bacteria, and cellular organelles. These models, composed of thousands of macromolecules and billions of atoms, have historically posed significant challenges for manipulation and visualization without specialized molecular graphics tools and hardware. With the recent advancements in GPU rendering power and web browser capabilities, it is now feasible to render interactively large molecular scenes directly on the web. In this work, we introduce Mesoscale Explorer, a web application built using the Mol* framework, dedicated to the visualization of large-scale molecular models ranging from viruses to cell organelles. Mesoscale Explorer provides unprecedented access and insight into the molecular fabric of life, enhancing perception, streamlining exploration, and simplifying visualization of diverse data types, showcasing the intricate details of these models with unparalleled clarity.

• Klíčová slova
• 3D animation, interactive tours, mesoscale models, molecular graphism, web‐based 3D visualization,
• MeSH
• elektronová kryomikroskopie * metody   MeSH
• molekulární modely * MeSH
• software * MeSH
• viry chemie   ultrastruktura   MeSH
• Publikační typ
• časopisecké články MeSH

The advent of cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), coupled with computational modeling, has enabled the creation of integrative 3D models of viruses, bacteria, and cellular organelles. These models, composed of thousands of macromolecules and billions of atoms, have historically posed significant challenges for manipulation and visualization without specialized molecular graphics tools and hardware. With the recent advancements in GPU rendering power and web browser capabilities, it is now feasible to render interactively large molecular scenes directly on the web. In this work, we introduce Mesoscale Explorer, a web application built using the Mol* framework, dedicated to the visualization of large-scale molecular models ranging from viruses to cell organelles. Mesoscale Explorer provides unprecedented access and insight into the molecular fabric of life, enhancing perception, streamlining exploration, and simplifying visualization of diverse data types, showcasing the intricate details of these models with unparalleled clarity.

• Klíčová slova
• 3D animation, interactive tours, mesoscale models, molecular graphism, web-based 3D visualization,
• Publikační typ
• časopisecké články MeSH
• preprinty MeSH

Homology modeling is a method for building protein 3D structures using protein primary sequence and utilizing prior knowledge gained from structural similarities with other proteins. The homology modeling process is done in sequential steps where sequence/structure alignment is optimized, then a backbone is built and later, side-chains are added. Once the low-homology loops are modeled, the whole 3D structure is optimized and validated. In the past three decades, a few collective and collaborative initiatives allowed for continuous progress in both homology and ab initio modeling. Critical Assessment of protein Structure Prediction (CASP) is a worldwide community experiment that has historically recorded the progress in this field. Folding@Home and Rosetta@Home are examples of crowd-sourcing initiatives where the community is sharing computational resources, whereas RosettaCommons is an example of an initiative where a community is sharing a codebase for the development of computational algorithms. Foldit is another initiative where participants compete with each other in a protein folding video game to predict 3D structure. In the past few years, contact maps deep machine learning was introduced to the 3D structure prediction process, adding more information and increasing the accuracy of models significantly. In this review, we will take the reader in a journey of exploration from the beginnings to the most recent turnabouts, which have revolutionized the field of homology modeling. Moreover, we discuss the new trends emerging in this rapidly growing field.

• Klíčová slova
• Artificial intelligence, Collective intelligence, Homology modeling, Machine learning, Protein 3D structure, Structural bioinformatics,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PDBsum is a web server providing structural information on the entries in the Protein Data Bank (PDB). The analyses are primarily image-based and include protein secondary structure, protein-ligand and protein-DNA interactions, PROCHECK analyses of structural quality, and many others. The 3D structures can be viewed interactively in RasMol, PyMOL, and a JavaScript viewer called 3Dmol.js. Users can upload their own PDB files and obtain a set of password-protected PDBsum analyses for each. The server is freely accessible to all at: http://www.ebi.ac.uk/pdbsum.

• Klíčová slova
• 3D protein structure, PDB, PDBsum, enzymes, molecular interactions, protein database, protein structure analysis, schematic diagrams,
• MeSH
• databáze proteinů * MeSH
• internet * MeSH
• molekulární modely * MeSH
• sekundární struktura proteinů * MeSH
• software * MeSH
• zobrazování trojrozměrné * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We describe the synthesis, pharmacological properties, and structures of antidiuretic agonists, arginine vasopressin (AVP) and [D-Arg(8)]-vasopressin (DAVP), and their inverso analogues. The structures of the peptides are studied based on micellar and liposomic models of cell membranes using CD spectroscopy. Additionally, three-dimensional structures in mixed anionic-zwitterionic micelles are obtained using NMR spectroscopy and molecular dynamics simulations. NMR data have shown that AVP and DAVP tend to adopt typical of vasopressin-like peptides β-turns: in the 2-5 and 3-6 fragments. The inverso-analogues also adopt β-turns in the 3-6 fragments. For this reason, their inactivity seems to be due to the difference in side chains orientations of Tyr(2), Phe(3), and Arg(8), important for interactions with the receptors. Again, the potent antidiuretic activity of DAVP can be explained by CD data suggesting differences in mutual arrangement of the aromatic side chains of Tyr(2) and Phe(3) in this peptide in liposomes rather than of native AVP. In the presence of liposomes, the smallest conformational changes of the peptides are noticed with DPPC and the largest with DPPG liposomes. This suggests that electrostatic interactions are crucial for the peptide-membrane interactions. We obtained similar, probably active, conformations of the antidiuretic agonists in the mixed DPC/SDS micelles (5:1) and in the mixed DPPC/DPPG (7:3) liposomes. Thus it can be speculated that the anionic-zwitterionic liposomes as well as the anionic-zwitterionic micelles, mimicking the eukaryotic cell membrane environment, partially restrict conformational freedom of the peptides and probably induce conformations resembling those of biologically relevant ones.

• Klíčová slova
• Anionic–zwitterionic micelles, Antidiuretic agonists, Inverso analogues, Liposomes,
• MeSH
• antidiuretika chemická syntéza   chemie   farmakologie   MeSH
• arginin vasopresin analogy a deriváty   chemická syntéza   chemie   farmakologie   MeSH
• buněčná membrána chemie   účinky léků   MeSH
• krysa rodu Rattus MeSH
• liposomy chemie   MeSH
• micely * MeSH
• molekulární sekvence - údaje MeSH
• peptidy chemie   MeSH
• potkani Wistar MeSH
• sekvence aminokyselin MeSH
• simulace molekulární dynamiky * MeSH
• terciární struktura proteinů MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antidiuretika MeSH
• arginin vasopresin MeSH
• liposomy MeSH
• micely * MeSH
• peptidy MeSH

Skeletal ciliopathies are a heterogeneous group of autosomal recessive osteochondrodysplasias caused by defects in formation, maintenance and function of the primary cilium. Mutations in the underlying genes affect the molecular motors, intraflagellar transport complexes (IFT), or the basal body. The more severe phenotypes are caused by defects of genes of the dynein-2 complex, where mutations in DYNC2H1, WDR34 and WDR60 have been identified. In a patient with a Jeune-like phenotype we performed exome sequencing and identified compound heterozygous missense and nonsense mutations in DYNC2LI1 segregating with the phenotype. DYNC2LI1 is ubiquitously expressed and interacts with DYNC2H1 to form the dynein-2 complex important for retrograde IFT. Using DYNC2LI1 siRNA knockdown in fibroblasts we identified a significantly reduced cilia length proposed to affect cilia function. In addition, depletion of DYNC2LI1 induced altered cilia morphology with broadened ciliary tips and accumulation of IFT-B complex proteins in accordance with retrograde IFT defects. Our results expand the clinical spectrum of ciliopathies caused by defects of the dynein-2 complex.

• MeSH
• cilie metabolismus   MeSH
• cytoplazmatické dyneiny chemie   genetika   MeSH
• exom genetika   MeSH
• fibroblasty metabolismus   MeSH
• fluorescenční protilátková technika MeSH
• heterozygot MeSH
• lidé MeSH
• mutace genetika   MeSH
• nesmyslný kodon genetika   MeSH
• sekvenční analýza DNA MeSH
• terciární struktura proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytoplazmatické dyneiny MeSH
• DYNC2LI1 protein, human MeSH Prohlížeč
• nesmyslný kodon MeSH

PDBsum, http://www.ebi.ac.uk/pdbsum, is a website providing numerous pictorial analyses of each entry in the Protein Data Bank. It portrays the structural features of all proteins, DNA and ligands in the entry, as well as depicting the interactions between them. The latest features, described here, include annotation of human protein sequences with their naturally occurring amino acid variants, dynamic graphs showing the relationships between related protein domain architectures, analyses of ligand binding clusters across different experimental determinations of the same protein, analyses of tunnels in proteins and new search options.

• MeSH
• databáze proteinů * MeSH
• genetická variace MeSH
• internet MeSH
• konformace proteinů * MeSH
• lidé MeSH
• ligandy MeSH
• počítačová grafika MeSH
• proteiny chemie   genetika   MeSH
• racionální návrh léčiv MeSH
• shluková analýza MeSH
• terciární struktura proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• ligandy MeSH
• proteiny MeSH

Accumulation of reduced pheophytin a (Pheo-D1) in photosystem II reaction center (PSII RC) under illumination at low redox potential is accompanied by changes in absorbance and circular dichroism spectra. The temperature dependences of these spectral changes have the potential to distinguish between changes caused by the excitonic interaction and temperature-dependent processes. We observed a conformational change in the PSII RC protein part and changes in the spatial positions of the PSII RC pigments of the active D1 branch upon reduction of Pheo-D1 only in the case of high temperature (298 K) dynamics. The resulting absorption difference spectra of PSII RC models equilibrated at temperatures of 77 K and 298 K were highly consistent with our previous experiments in which light-induced bleaching of the PSII RC absorbance spectrum was observable only at 298 K. These results support our previous hypothesis that Pheo-D1 does not interact excitonically with the other chlorins of the PSII RC, since the reduced form of Pheo-D1 causes absorption spectra bleaching only due to temperature-dependent processes.

• MeSH
• bakteriální proteiny chemie   metabolismus   MeSH
• fotosystém II (proteinový komplex) chemie   metabolismus   MeSH
• konformace proteinů účinky záření   MeSH
• molekulární modely MeSH
• oxidace-redukce účinky záření   MeSH
• sinice metabolismus   MeSH
• spektrofotometrie metody   MeSH
• světlo * MeSH
• vysoká teplota MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bakteriální proteiny MeSH
• fotosystém II (proteinový komplex) MeSH
• photosystem II, psbA subunit MeSH Prohlížeč