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LiteMol suite is an innovative solution that enables near-instant delivery of model and experimental biomacromolecular structural data, providing users with an interactive and responsive experience in all modern web browsers and mobile devices. LiteMol suite is a combination of data delivery services (CoordinateServer and DensityServer), compression format (BinaryCIF), and a molecular viewer (LiteMol Viewer). The LiteMol suite is integrated into Protein Data Bank in Europe (PDBe) and other life science web applications (e.g., UniProt, Ensemble, SIB, and CNRS services), it is freely available at https://litemol.org , and its source code is available via GitHub. LiteMol suite provides advanced functionality (annotations and their visualization, powerful selection features), and this chapter will describe their use for visual inspection of protein structures.

Secondary structure elements (SSEs) are inherent parts of protein structures, and their arrangement is characteristic for each protein family. Therefore, annotation of SSEs can facilitate orientation in the vast number of homologous structures which is now available for many protein families. It also provides a way to identify and annotate the key regions, like active sites and channels, and subsequently answer the key research questions, such as understanding of molecular function and its variability.This chapter introduces the concept of SSE annotation and describes the workflow for obtaining SSE annotation for the members of a selected protein family using program SecStrAnnotator.

We have performed a study of quantum turbulence generated in oscillatory counterflow as a continuation of previous experiments on various channel flows of superfluid helium, in the form of coflow, thermal DC counterflow and pure superflow. We have investigated its development, steady state properties and temporal decay, as well as the effect of the resonant mode used to generate the turbulence at three different temperatures, 1.45 K, 1.65 K and 1.83 K. The attenuation of low amplitude second sound, orientated perpendicularly to the long axis of the resonator, was used to determine the amount of quantized vortices created. One of the main goals of this work was to characterize the critical parameters for the onset of instabilities in oscillatory counterflow and to determine their values. Decay measurements of the vortex line density allowed us to distinguish between Vinen-type and Kolmogorov- type decays of quantum turbulence.

Secondary structure elements (SSEs) are inherent parts of protein structures, and their arrangement is characteristic for each protein family. Therefore, annotation of SSEs can facilitate orientation in the vast number of homologous structures which is now available for many protein families. It also provides a way to identify and annotate the key regions, like active sites and channels, and subsequently answer the key research questions, such as understanding of molecular function and its variability. This chapter introduces the concept of SSE annotation and describes the workflow for obtaining SSE annotation for the members of a selected protein family using program SecStrAnnotator.

Selected benzo[c]phenathridine alkaloids were biotransformed using rat liver microsomes and identified by liquid chromatography and mass spectrometry. While the metabolites of commercially available sanguinarine and chelerythrine have been studied in detail, data about the metabolism of the minor alkaloids remained unknown. Reactions involved in transformation include single and/or double O-demethylation, demethylenation, reduction, and hydroxylation. Two metabolites, when isolated, purified and tested for toxicity, were found to be less toxic than the original compounds.

The principal aim of this Thesis is the construction of a cryogenic setup for the investigation of quantum turbulence in superfluid helium (He II) using microresonators and a to perform a study of the transition to turbulence in oscillatory flow of He II in the temperature range from 2.170 K down to 1.293 K. We have designed and constructed a setup consisting of a superconducting vibrating microwire and a so-called fountain pump, and, after initial testing and characterization, used it to probe the instabilities occurring in the flow of He II. Specifically, we were interested in the origin of the instabilities in the flow around the microwire and in the question whether they originate mostly from classical-like flow of the normal component, as is often the case with the well-known tuning forks, or whether they are related to the generation of quantized vortices in the superfluid component of He II. To distinguish between these two types of instabilities, we have derived from the Navier-Stokes equations scaling laws related to drag forces in classical oscillatory flow, which we have applied to the normal component of superfluid helium. This also enabled us to verify the validity of the high-frequency limit of oscillatory flow for the case of the microwire. Finally, we have examined the capability of the...

Composition and organization of secondary structure elements (SSEs), such as alpha-helices and beta-sheets, are characteristic for protein families and they participate in formation of protein fold. They are however often influenced by the sequence variability and ligand binding. For this reason, identification of similarities and differences between SSEs can help us in the analysis of individual proteins within a protein family. To utilize the SSEs for research of individual protein families, we need to have the SSEs easily and automatically intercomparable within one protein family. Specifically, the corresponding SSEs should have the same name (annotation) and there should be a transparent schema of their localization in the protein structures. Unfortunately, SSE annotations are still performed mainly manually and universal automatic approach to assign SSE names is not available yet. Moreover, current methods focused on 2D visualization of SSEs (e.g., PROMOTIF, Pro-origami, HERA) do not consider information about real distances of SSEs. Therefore, even when two proteins from the same family differ only slightly, their SSE 2D diagrams can be totally different. For this reason, we developed a tool set which can perform SSE annotation and 2D visualization in such a way that structural information is kept. Applicability of this approach is shown in a case study focused on cytochromes P450. This protein family of drug-metabolizing enzymes has currently available more than 750 structures from about 30 organisms and each cytochrome P450 contains more than 20 SSEs for which there is a stable annotation used through the community. Our approach can be further extended to other protein structural families, which will allow family-wide SSE annotations and comparisons in a simple visual manner.

Recent advances in Cryo-EM and other structure determination techniques enabled a rapid increase in the complexity and size of biomacromolecular structures available in the Protein Data Bank (PDB). A great challenge is to deliver and visualize this data to the user in a reasonable time. Until now, Java-based applets such as Jmol have served this purpose. However, the lack of support for Java applets in the web browsers and introduction of HTML5 and WebGL web frameworks provide an opportunity to develop better solutions to address this problem.We have developed a comprehensive solution for both efficient delivery of large data sets and interactive visualisation of macromolecular structures.The CoordinateServer (https://www.ebi.ac.uk/pdbe/coordinates) provides functionality for dynamic selection of a subset of structural data (backbone, ligand binding sites, etc.) that is of interest to the user. The amount of transferred data is further reduced using binary representation of the standard mmCIF data format called BinaryCIF. The CoordinateServer thus provides a complete solution for efficient transfer of data to user interface.LiteMol (http://ncbr.muni.cz/LiteMol) is an interactive browser based 3D viewer, designed using HTML5 and WebGL technologies that provides all key structural visualisation modes. The viewer also integrates PDBe REST API services (http://pdbe.org/api) to show biomacromolecular annotations (validation, sequence annotation). LiteMol can use the standard mmCIF files or the CoordinateServer for fast data access. Thanks to integration with the CoordinateServer, LiteMol can generate an interactive 3D display for the largest currently available structure, the HIV capsid with 2.4 million atoms, in less than a minute. LiteMol is integrated into PDBe entry pages (e.g. http://www.ebi.ac.uk/pdbe/entry/pdb/1cbs/bound/REA) and can, for the first time, show the electron density maps online in an interactive way. We are collaborating with UniProt, OpenTargets, and Glycopedia teams to integrate LiteMol into their pages.

The main goal of this Thesis was to develop and optimize fitting procedures for the detailed modeling of resonant curves characterizing physical behaviour of micron sized electro-mechanical resonators (MEMS). These devices are frequently used for the detec- tion of hydrodynamical properties of quantum fluids such as He II. We provide the model originating from the equation of motion of linear harmonic oscillator introducing extra parameters describing nonlinear drag forces and nonlinear restoring force. By testing of our fitting procedures on the real measured experimental data, we verify their applica- bility. For this purpose we chose two types of experiments namely; resonant behaviour of silicon vibrating wires measured at sub-kelvin temperatures in vacuum omitting any nonlinear drag and; resonant behaviour of NbTi vibrating wire submerged in superfluid helium at 1K experiencing both types of nonlinearities. Presented results prove universal- ity and robustness of developed procedures and are able to capture physical effects such as turbulent transition in a flow past the oscillating body or the Duffing like nonlinearity. 1

The main goal of this Thesis was the manufacture and characterisation of a new type of local probe of quantum turbulence in He II. Our MEMS devices are semicircular loops 3 mm in diameter made of 40 µm superconducting NbTi wire placed in magnetic field, whose motion is driven by applied alternating current. To detect quantum turbulence, we measure the hydrodynamic properties of the probe, in particular changes in its reso- nant frequency and amplitude depending on the applied external flow. In this work we specifically investigate the generation of quantum turbulence in thermal counterflow of He II for temperatures between 1.45 K and 2.1 K, representing a well-known and under- stood system suitable for the characterisation of our devices. Additionally, the response of the detectors is calibrated against the intensity of turbulence as given by the vortex line density L, measured simultaneously using second sound attenuation. This technique is more sensitive than the microresonators, but precludes any attempts at local detection of L necessary to study inhomogeneous systems of quantized vortices. Analysis of the results based on the Donnelly number describing instabilities in the normal component has confirmed the sensitivity of the probe to quantized vortices in the superfluid. 1