SUMMARY: MOLEonline is an interactive, web-based tool designed to detect and analyse channels (pores and tunnels) within protein structures. The latest version of MOLEonline addresses the limitations of its predecessor by integrating the Mol* viewer for visualization and offering a streamlined, fully interactive user experience. The new features include colouring tunnels in the 3D viewer based on their physicochemical properties. A 2D representation of the protein structure and calculated tunnels is generated using 2DProts. Users can now store tunnels directly in the mmCIF file format, facilitating sharing via the community-standard FAIR format for structural data. In addition, the ability to store and load computation settings ensures the reproducibility of tunnel computation results. Integration with the ChannelsDB 2.0 database allows users to access precomputed tunnels. AVAILABILITY AND IMPLEMENTATION: The MOLEonline application is freely available at https://moleonline.cz with no login requirement, its source code is stored at GitHub under the MIT licence at https://github.com/sb-ncbr/moleonline-web, and archived at Figshare at https://doi.org/10.6084/m9.figshare.29816174.

• MeSH
• Databases, Protein MeSH
• Internet MeSH
• Protein Conformation MeSH
• Proteins * chemistry   MeSH
• Software * MeSH
• User-Computer Interface MeSH
• Computational Biology * methods   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Proteins * MeSH

ChannelsDB 2.0 is an updated database providing structural information about the position, geometry and physicochemical properties of protein channels-tunnels and pores-within deposited biomacromolecular structures from PDB and AlphaFoldDB databases. The newly deposited information originated from several sources. Firstly, we included data calculated using a popular CAVER tool to complement the data obtained using original MOLE tool for detection and analysis of protein tunnels and pores. Secondly, we added tunnels starting from cofactors within the AlphaFill database to enlarge the scope of the database to protein models based on Uniprot. This has enlarged available channel annotations ∼4.6 times as of 1 September 2023. The database stores information about geometrical features, e.g. length and radius, and physico-chemical properties based on channel-lining amino acids. The stored data are interlinked with the available UniProt mutation annotation data. ChannelsDB 2.0 provides an excellent resource for deep analysis of the role of biomacromolecular tunnels and pores. The database is available free of charge: https://channelsdb2.biodata.ceitec.cz.

• MeSH
• Amino Acids MeSH
• Databases, Protein * MeSH
• Protein Conformation MeSH
• Proteins * chemistry   MeSH
• Software * MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amino Acids MeSH
• Proteins * MeSH

Caver Web 1.0 is a web server for comprehensive analysis of protein tunnels and channels, and study of the ligands' transport through these transport pathways. Caver Web is the first interactive tool allowing both the analyses within a single graphical user interface. The server is built on top of the abundantly used tunnel detection tool Caver 3.02 and CaverDock 1.0 enabling the study of the ligand transport. The program is easy-to-use as the only required inputs are a protein structure for a tunnel identification and a list of ligands for the transport analysis. The automated guidance procedures assist the users to set up the calculation in a way to obtain biologically relevant results. The identified tunnels, their properties, energy profiles and trajectories for ligands' passages can be calculated and visualized. The tool is very fast (2-20 min per job) and is applicable even for virtual screening purposes. Its simple setup and comprehensive graphical user interface make the tool accessible for a broad scientific community. The server is freely available at https://loschmidt.chemi.muni.cz/caverweb.

• MeSH
• Algorithms * MeSH
• Benchmarking MeSH
• Protein Interaction Domains and Motifs MeSH
• Internet MeSH
• Protein Structure, Quaternary MeSH
• Humans MeSH
• Ligands MeSH
• Amino Acid Sequence MeSH
• Molecular Docking Simulation MeSH
• Protein Structure, Tertiary MeSH
• Carrier Proteins chemistry   metabolism   MeSH
• User-Computer Interface * MeSH
• Protein Binding MeSH
• Binding Sites MeSH
• Computational Biology methods   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Ligands MeSH
• Carrier Proteins MeSH

MOLEonline is an interactive, web-based application for the detection and characterization of channels (pores and tunnels) within biomacromolecular structures. The updated version of MOLEonline overcomes limitations of the previous version by incorporating the recently developed LiteMol Viewer visualization engine and providing a simple, fully interactive user experience. The application enables two modes of calculation: one is dedicated to the analysis of channels while the other was specifically designed for transmembrane pores. As the application can use both PDB and mmCIF formats, it can be leveraged to analyze a wide spectrum of biomacromolecular structures, e.g. stemming from NMR, X-ray and cryo-EM techniques. The tool is interconnected with other bioinformatics tools (e.g., PDBe, CSA, ChannelsDB, OPM, UniProt) to help both setup and the analysis of acquired results. MOLEonline provides unprecedented analytics for the detection and structural characterization of channels, as well as information about their numerous physicochemical features. Here we present the application of MOLEonline for structural analyses of α-hemolysin and transient receptor potential mucolipin 1 (TRMP1) pores. The MOLEonline application is freely available via the Internet at https://mole.upol.cz.

• MeSH
• Internet * MeSH
• Protein Conformation * MeSH
• Models, Molecular MeSH
• Software * MeSH
• Computational Biology * MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

ChannelsDB (http://ncbr.muni.cz/ChannelsDB) is a database providing information about the positions, geometry and physicochemical properties of channels (pores and tunnels) found within biomacromolecular structures deposited in the Protein Data Bank. Channels were deposited from two sources; from literature using manual deposition and from a software tool automatically detecting tunnels leading to the enzymatic active sites and selected cofactors, and transmembrane pores. The database stores information about geometrical features (e.g. length and radius profile along a channel) and physicochemical properties involving polarity, hydrophobicity, hydropathy, charge and mutability. The stored data are interlinked with available UniProt annotation data mapping known mutation effects to channel-lining residues. All structures with channels are displayed in a clear interactive manner, further facilitating data manipulation and interpretation. As such, ChannelsDB provides an invaluable resource for research related to deciphering the biological function of biomacromolecular channels.

• MeSH
• Amino Acids chemistry   metabolism   MeSH
• Cytochrome P-450 CYP2D6 chemistry   genetics   metabolism   MeSH
• Databases, Protein * MeSH
• Eukaryotic Cells cytology   enzymology   MeSH
• Gene Expression MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Ion Channels chemistry   genetics   metabolism   MeSH
• Nuclear Pore chemistry   genetics   metabolism   MeSH
• Catalytic Domain MeSH
• Coenzymes chemistry   metabolism   MeSH
• Humans MeSH
• Mutation MeSH
• Prokaryotic Cells cytology   enzymology   MeSH
• Software * MeSH
• Static Electricity MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amino Acids MeSH
• Cytochrome P-450 CYP2D6 MeSH
• Ion Channels MeSH
• Coenzymes 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.

• Keywords
• 3D protein structure, PDB, PDBsum, enzymes, molecular interactions, protein database, protein structure analysis, schematic diagrams,
• MeSH
• Databases, Protein * MeSH
• Internet * MeSH
• Models, Molecular * MeSH
• Protein Structure, Secondary * MeSH
• Software * MeSH
• Imaging, Three-Dimensional * MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Protein structures and their interaction with ligands have been in the focus of biochemistry and structural biology research for decades. The transportation of ligand into the protein active site is often complex process, driven by geometric and physico-chemical properties, which renders the ligand path full of jitter and impasses. This prevents understanding of the ligand transportation and reasoning behind its behavior along the path. RESULTS: To address the needs of the domain experts we design an explorative visualization solution based on a multi-scale simplification model. It helps to navigate the user to the most interesting parts of the ligand trajectory by exploring different attributes of the ligand and its movement, such as its distance to the active site, changes of amino acids lining the ligand, or ligand "stuckness". The process is supported by three linked views - 3D representation of the simplified trajectory, scatterplot matrix, and bar charts with line representation of ligand-lining amino acids. CONCLUSIONS: The usage of our tool is demonstrated on molecular dynamics simulations provided by the domain experts. The tool was tested by the domain experts from protein engineering and the results confirm that it helps to navigate the user to the most interesting parts of the ligand trajectory and to understand the ligand behavior.

• Keywords
• Bioinformatics visualization, Computational proteomics, Molecular visualization,
• MeSH
• Amino Acids chemistry   MeSH
• Catalytic Domain MeSH
• Protein Conformation MeSH
• Ligands MeSH
• Models, Molecular MeSH
• Image Processing, Computer-Assisted MeSH
• Proteins chemistry   MeSH
• Molecular Dynamics Simulation * MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amino Acids MeSH
• Ligands MeSH
• Proteins MeSH

Yellow-related proteins (YRPs) present in sand fly saliva act as affinity binders of bioamines, and help the fly to complete a bloodmeal by scavenging the physiological signals of damaged cells. They are also the main antigens in sand fly saliva and their recombinant form is used as a marker of host exposure to sand flies. Moreover, several salivary proteins and plasmids coding these proteins induce strong immune response in hosts bitten by sand flies and are being used to design protecting vaccines against Leishmania parasites. In this study, thirty two 3D models of different yellow-related proteins from thirteen sand fly species of two genera were constructed based on the known protein structure from Lutzomyia longipalpis. We also studied evolutionary relationships among species based on protein sequences as well as sequence and structural variability of their ligand-binding site. All of these 33 sand fly YRPs shared a similar structure, including a unique tunnel that connects the ligand-binding site with the solvent by two independent paths. However, intraspecific modifications found among these proteins affects the charges of the entrances to the tunnel, the length of the tunnel and its hydrophobicity. We suggest that these structural and sequential differences influence the ligand-binding abilities of these proteins and provide sand flies with a greater number of YRP paralogs with more nuanced answers to bioamines. All these characteristics allow us to better evaluate these proteins with respect to their potential use as part of anti-Leishmania vaccines or as an antigen to measure host exposure to sand flies.

• MeSH
• Phylogeny MeSH
• Glycosylation MeSH
• Insect Proteins chemistry   metabolism   MeSH
• Protein Conformation MeSH
• Ligands MeSH
• Models, Molecular MeSH
• Psychodidae * MeSH
• Amino Acid Sequence MeSH
• Saliva metabolism   MeSH
• Static Electricity MeSH
• Binding Sites MeSH
• Hydrogen Bonding MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Insect Proteins MeSH
• Ligands MeSH

The Eighth Central European Conference "Chemistry towards Biology" was held in Brno, Czech Republic, on August 28-September 1, 2016 to bring together experts in biology, chemistry and design of bioactive compounds; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topics of the conference covered "Chemistry towards Biology", meaning that the event welcomed chemists working on biology-related problems, biologists using chemical methods, and students and other researchers of the respective areas that fall within the common scope of chemistry and biology. The authors of this manuscript are plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting.

• Keywords
• ADME, drug delivery systems, biological chemistry, biomaterials, chemical biology, drug design, nanoparticles, natural compounds, proteins and nucleic acids, synthesis, targeting,
• MeSH
• Epigenesis, Genetic MeSH
• Chemistry, Pharmaceutical methods   MeSH
• Drug Delivery Systems MeSH
• Proteins chemistry   MeSH
• Drug Design MeSH
• Systems Biology MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Congress MeSH
• Names of Substances
• Proteins MeSH

BACKGROUND: Enzyme active sites can be connected to the exterior environment by one or more channels passing through the protein. Despite our current knowledge of enzyme structure and function, surprisingly little is known about how often channels are present or about any structural features such channels may have in common. RESULTS: Here, we analyze the long channels (i.e. >15 Å) leading to the active sites of 4,306 enzyme structures. We find that over 64% of enzymes contain two or more long channels, their typical length being 28 Å. We show that amino acid compositions of the channel significantly differ both to the composition of the active site, surface and interior of the protein. CONCLUSIONS: The majority of enzymes have buried active sites accessible via a network of access channels. This indicates that enzymes tend to have buried active sites, with channels controlling access to, and egress from, them, and that suggests channels may play a key role in helping determine enzyme substrate.

• MeSH
• Amino Acids chemistry   genetics   MeSH
• Enzymes chemistry   genetics   MeSH
• Ion Channels physiology   MeSH
• Catalytic Domain MeSH
• Protein Conformation MeSH
• Humans MeSH
• Models, Molecular MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amino Acids MeSH
• Enzymes MeSH
• Ion Channels MeSH