With the ever-expanding toolkit of molecular viewers, the ability to visualize macromolecular structures has never been more accessible. Yet, the idiosyncratic technical intricacies across tools and the integration complexities associated with handling structure annotation data present significant barriers to seamless interoperability and steep learning curves for many users. The necessity for reproducible data visualizations is at the forefront of the current challenges. Recently, we introduced MolViewSpec (homepage: https://molstar.org/mol-view-spec/, GitHub project: https://github.com/molstar/mol-view-spec), a specification approach that defines molecular visualizations, decoupling them from the varying implementation details of different molecular viewers. Through the protocols presented herein, we demonstrate how to use MolViewSpec and its 3D view-building Python library for creating sophisticated, customized 3D views covering all standard molecular visualizations. MolViewSpec supports representations like cartoon and ball-and-stick with coloring, labeling, and applying complex transformations such as superposition to any macromolecular structure file in mmCIF, BinaryCIF, and PDB formats. These examples showcase progress towards reusability and interoperability of molecular 3D visualization in an era when handling molecular structures at scale is a timely and pressing matter in structural bioinformatics as well as research and education across the life sciences. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Creating a MolViewSpec view using the MolViewSpec Python package Basic Protocol 2: Creating a MolViewSpec view with reference to MolViewSpec annotation files Basic Protocol 3: Creating a MolViewSpec view with labels and other advanced features Support Protocol 1: Computing rotation and translation vectors Support Protocol 2: Creating a MolViewSpec annotation file.

• Klíčová slova
• 3D visualization, Protein Data Bank, interoperability, macromolecular structure, mmCIF,
• MeSH
• makromolekulární látky chemie   MeSH
• molekulární modely MeSH
• software * MeSH
• zobrazování trojrozměrné MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• makromolekulární látky MeSH

PURPOSE: To understand how macromolecular content varies in the human brain with age in a large cohort of healthy subjects. METHODS: In-vivo 1H-MR spectra were acquired using ultra-short TE STEAM at 7T in the posterior cingulate cortex. Macromolecular content was studied in 147 datasets from a cohort ranging in age from 19 to 89 y. Three fitting approaches were used to evaluate the macromolecular content: (1) a macromolecular resonances model developed for this study; (2) LCModel-simulated macromolecules; and (3) a combination of measured and LCModel-simulated macromolecules. The effect of age on the macromolecular content was investigated by considering age both as a continuous variable (i.e., linear regressions) and as a categorical variable (i.e., multiple comparisons among sub-groups obtained by stratifying data according to age by decade). RESULTS: While weak age-related effects were observed for macromolecular peaks at ˜0.9 (MM09), ˜1.2 (MM12), and ˜1.4 (MM14) ppm, moderate to strong effects were observed for peaks at ˜1.7 (MM17), and ˜2.0 (MM20) ppm. Significantly higher MM17 and MM20 content started from 30 to 40 y of age, while for MM09, MM12, and MM14, significantly higher content started from 60 to 70 y of age. CONCLUSIONS: Our findings provide insights into age-related differences in macromolecular contents and strengthen the necessity of using age-matched measured macromolecules during quantification.

• Klíčová slova
• LCModel, MRS, aging, macromolecules, ultra‐high field,
• MeSH
• cingulární gyrus diagnostické zobrazování   chemie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• magnetická rezonanční tomografie metody   MeSH
• makromolekulární látky * chemie   MeSH
• mladý dospělý MeSH
• mozek diagnostické zobrazování   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stárnutí * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• makromolekulární látky * MeSH

Single particle analysis (SPA) in cryo-electron microscopy (cryo-EM) is highly used to obtain the near-atomic structure of biological macromolecules. The current methods allow users to produce high-resolution maps from many samples. However, there are still challenging cases that require extra processing to obtain high resolution. This is the case when the macromolecule of the sample is composed of different components and we want to focus just on one of them. For example, if the macromolecule is composed of several flexible subunits and we are interested in a specific one, if it is embedded in a viral capsid environment, or if it has additional components to stabilize it, such as nanodiscs. The signal from these components, which in principle we are not interested in, can be removed from the particles using a projection subtraction method. Currently, there are two projection subtraction methods used in practice and both have some limitations. In fact, after evaluating their results, we consider that the problem is still open to new solutions, as they do not fully remove the signal of the components that are not of interest. Our aim is to develop a new and more precise projection subtraction method, improving the performance of state-of-the-art methods. We tested our algorithm with data from public databases and an in-house data set. In this work, we show that the performance of our algorithm improves the results obtained by others, including the localization of small ligands, such as drugs, whose binding location is unknown a priori.

• Klíčová slova
• Cryo-EM, Ligand, Nanodisc, Projection subtraction, SPA,
• MeSH
• algoritmy * MeSH
• elektronová kryomikroskopie metody   MeSH
• makromolekulární látky chemie   MeSH
• zobrazení jednotlivé molekuly * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• makromolekulární látky MeSH

One of the main purposes of CryoEM Single Particle Analysis is to reconstruct the three-dimensional structure of a macromolecule thanks to the acquisition of many particle images representing different poses of the sample. By estimating the orientation of each projected particle, it is possible to recover the underlying 3D volume by multiple 3D reconstruction methods, usually working either in Fourier or in real space. However, the reconstruction from the projected images works under the assumption that all particles in the dataset correspond to the same conformation of the macromolecule. Although this requisite holds for some macromolecules, it is not true for flexible specimens, leading to motion-induced artefacts in the reconstructed CryoEM maps. In this work, we introduce a new Algebraic Reconstruction Technique called ZART, which is able to include continuous flexibility information during the reconstruction process to improve local resolution and reduce motion blurring. The conformational changes are modelled through Zernike3D polynomials. Our implementation allows for a multiresolution description of the macromolecule adapting itself to the local resolution of the reconstructed map. In addition, ZART has also proven to be a useful algorithm in cases where flexibility is not so dominant, as it improves the overall aspect of the reconstructed maps by improving their local and global resolution.

• Klíčová slova
• Cryo-Electron Microscopy (CryoEM), Zernike polynomials, Zernike3D-based Algebraic Reconstruction Technique (ZART), map reconstruction, spherical harmonics,
• MeSH
• algoritmy MeSH
• elektronová kryomikroskopie metody   MeSH
• makromolekulární látky chemie   MeSH
• počítačové zpracování obrazu * metody   MeSH
• pohyb těles MeSH
• zobrazení jednotlivé molekuly * MeSH
• zobrazování trojrozměrné metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• makromolekulární látky MeSH

The new developments in Cryo-EM Single Particle Analysis are helping us to understand how the macromolecular structure and function meet to drive biological processes. By capturing many states at the particle level, it is possible to address how macromolecules explore different conformations, information that is classically extracted through 3D classification. However, the limitations of classical approaches prevent us from fully understanding the complete conformational landscape due to the reduced number of discrete states accurately reconstructed. To characterize the whole structural spectrum of a macromolecule, we propose an extension of our Zernike3D approach, able to extract per-image continuous flexibility information directly from a particle dataset. Also, our method can be seamlessly applied to images, maps or atomic models, opening integrative possibilities. Furthermore, we introduce the ZART reconstruction algorithm, which considers the Zernike3D deformation fields to revert particle conformational changes during the reconstruction process, thus minimizing the blurring induced by molecular motions.

• MeSH
• algoritmy * MeSH
• elektronová kryomikroskopie metody   MeSH
• makromolekulární látky chemie   MeSH
• molekulární konformace MeSH
• molekulární struktura MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• makromolekulární látky MeSH

Platinum-based anticancer drugs are actively developed utilizing lipophilic ligands or drug carriers for the efficient penetration of biomembranes, reduction of side effects, and tumor targeting. We report the development of a supramolecular host-guest system built on cationic platinum(II) compounds bearing ligands anchored in the cavity of the macrocyclic host. The host-guest binding and hydrolysis process on the platinum core were investigated in detail by using NMR, MS, X-ray diffraction, and relativistic DFT calculations. The encapsulation process in cucurbit[7]uril unequivocally promotes the stability of hydrolyzed dicationic cis-[PtII(NH3)2(H2O)(NH2-R)]2+ compared to its trans isomer. Biological screening on the ovarian cancer lines A2780 and A2780/CP shows time-dependent toxicity. Notably, the reported complex and its β-cyclodextrin (β-CD) assembly achieve the same cellular uptake as cisplatin and cisplatin@β-CD, respectively, while maintaining a significantly lower toxicity profile.

• MeSH
• lidé MeSH
• makrocyklické sloučeniny chemická syntéza   chemie   farmakologie   MeSH
• makromolekulární látky chemická syntéza   chemie   farmakologie   MeSH
• molekulární struktura MeSH
• nádorové buňky kultivované MeSH
• organoplatinové sloučeniny chemická syntéza   chemie   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky chemická syntéza   chemie   farmakologie   MeSH
• screeningové testy protinádorových léčiv MeSH
• teorie funkcionálu hustoty * MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• makrocyklické sloučeniny MeSH
• makromolekulární látky MeSH
• organoplatinové sloučeniny MeSH
• protinádorové látky MeSH

This paper summarizes the area of biomedicinal polymers, which serve as nanomedicines even though they do not contain any anticancer or antiinflammatory drugs. These polymer nanomedicines with unique design are in the literature highlighted as a novel class of therapeutics called "drug-free macromolecular therapeutics." Their therapeutic efficacy is based on the tailored multiple presentations of biologically active vectors, i.e., peptides, oligopeptides, or oligosaccharides. Thus, they enable, for example, to directly induce the apoptosis of malignant cells by the crosslinking of surface slowly internalizing receptors, or to deplete the efficacy of tumor-associated proteins. The precise biorecognition of natural binding motifs by multiple vectors on the polymer construct remains the crucial part in the designing of these drug-free nanomedicines. Here, the rationales, designs, synthetic approaches, and therapeutic potential of drug-free macromolecular therapeutics consisting of various active vectors are described in detail. Recent developments and achievements for namely B-cell lymphoma treatment, Gal-3-positive tumors, inflammative liver injury, and bacterial treatment are reviewed and highlighted. Finally, a possible future prospect within this highly exciting new field of nanomedicine research is presented.

• Klíčová slova
• drug-free macromolecular therapeutics, glycopolymers, nucleotides, peptides, polymers, saccharides,
• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• antiflogistika farmakologie   terapeutické užití   MeSH
• lékové transportní systémy metody   MeSH
• lidé MeSH
• makromolekulární látky chemie   MeSH
• nádory * farmakoterapie   MeSH
• nanomedicína metody   MeSH
• polymery chemie   MeSH
• protinádorové látky * farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky MeSH
• antiflogistika MeSH
• makromolekulární látky MeSH
• polymery MeSH
• protinádorové látky * MeSH

Large biomolecular structures are being determined experimentally on a daily basis using established techniques such as crystallography and electron microscopy. In addition, emerging integrative or hybrid methods (I/HM) are producing structural models of huge macromolecular machines and assemblies, sometimes containing 100s of millions of non-hydrogen atoms. The performance requirements for visualization and analysis tools delivering these data are increasing rapidly. Significant progress in developing online, web-native three-dimensional (3D) visualization tools was previously accomplished with the introduction of the LiteMol suite and NGL Viewers. Thereafter, Mol* development was jointly initiated by PDBe and RCSB PDB to combine and build on the strengths of LiteMol (developed by PDBe) and NGL (developed by RCSB PDB). The web-native Mol* Viewer enables 3D visualization and streaming of macromolecular coordinate and experimental data, together with capabilities for displaying structure quality, functional, or biological context annotations. High-performance graphics and data management allows users to simultaneously visualise up to hundreds of (superimposed) protein structures, stream molecular dynamics simulation trajectories, render cell-level models, or display huge I/HM structures. It is the primary 3D structure viewer used by PDBe and RCSB PDB. It can be easily integrated into third-party services. Mol* Viewer is open source and freely available at https://molstar.org/.

• MeSH
• internet MeSH
• konformace proteinů MeSH
• makromolekulární látky chemie   MeSH
• molekulární modely * MeSH
• software * 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
• makromolekulární látky MeSH

Lignohumate, as an industrially produced analog of natural humic substances, is studied from the point of view of its diffusion properties. This work focuses on its permeation ability, important in agricultural and horticultural applications, connected with its penetration into plant organs as leaves and roots. The hydrogel based on agarose was used as a model material for the diffusion of lignohumate. Two types of experiments were realized: the diffusion of lignohumate in the hydrogel diffusion couple and the diffusion of lignohumate from its solution into hydrogel. The diffusion coefficient of lignohumate in the hydrogel was determined and used for the modelling of the time development of concentration profiles. It was found that the model agrees with experimental data for short times but an accumulation of lignohumate in front of the interface between donor and acceptor hydrogels was observed after several days. The particle size distribution of lignohumate and changes in the E4/E6 ratio used as an indicator of molecular weight of humic substances were determined. The results showed that the supramolecular structure of lignohumate can react sensitively to actual changes in its environs and thus affect their mobility and permeability into different materials. A filtration effect at the interface can be observed as an accompanying phenomenon of the re-arrangement in the lignohumate secondary structure.

• Klíčová slova
• diffusion, hydrogel, lignohumate, spreading, supramolecular nature,
• MeSH
• algoritmy MeSH
• chemické jevy MeSH
• huminové látky analýza   MeSH
• hydrogely chemie   MeSH
• makromolekulární látky analýza   chemie   MeSH
• sefarosa chemie   MeSH
• teoretické modely MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• huminové látky MeSH
• hydrogely MeSH
• makromolekulární látky MeSH
• sefarosa MeSH

Biomacromolecular structural data make up a vital and crucial scientific resource that has grown not only in terms of its amount but also in its size and complexity. Furthermore, these data are accompanied by large and increasing amounts of experimental data. Additionally, the macromolecular data are enriched with value-added annotations describing their biological, physicochemical and structural properties. Today, the scientific community requires fast and fully interactive web visualization to exploit this complex structural information. This article provides a survey of the available cutting-edge web services that address this challenge. Specifically, it focuses on data-delivery problems, discusses the visualization of a single structure, including experimental data and annotations, and concludes with a focus on the results of molecular-dynamics simulations and the visualization of structural ensembles.

• Klíčová slova
• browser-based, data delivery, macromolecules, visualization, web-based,
• MeSH
• internet * MeSH
• makromolekulární látky chemie   MeSH
• počítačová grafika * MeSH
• software * MeSH
• uživatelské rozhraní počítače * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• makromolekulární látky MeSH