MDsrv: visual sharing and analysis of molecular dynamics simulations.

Molecular dynamics simulation is a proven technique for computing and visualizing the time-resolved motion of macromolecules at atomic resolution. The MDsrv is a tool that streams MD trajectories and displays them interactively in web browsers without requiring advanced skills, facilitating interactive exploration and collaborative visual analysis. We have now enhanced the MDsrv to further simplify the upload and sharing of MD trajectories and improve their online viewing and analysis.

High-performance macromolecular data delivery and visualization for the web. Corrigendum.

Two citations in the article by Sehnal et al. [(2020), Acta Cryst. D76, 1167-1173] are corrected.

Real-time structural motif searching in proteins using an inverted index strategy.

Biochemical and biological functions of proteins are the product of both the overall fold of the polypeptide chain, and, typically, structural motifs made up of smaller numbers of amino acids constituting a catalytic center or a binding site that may be remote from one another in amino acid sequence. Detection of such structural motifs can provide valuable insights into the function(s) of previously uncharacterized proteins. Technically, this remains an extremely challenging problem because of the size of the Protein Data Bank (PDB) archive.

High-performance macromolecular data delivery and visualization for the web.

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.

BinaryCIF and CIFTools-Lightweight, efficient and extensible macromolecular data management.

3D macromolecular structural data is growing ever more complex and plentiful in the wake of substantive advances in experimental and computational structure determination methods including macromolecular crystallography, cryo-electron microscopy, and integrative methods. Efficient means of working with 3D macromolecular structural data for archiving, analyses, and visualization are central to facilitating interoperability and reusability in compliance with the FAIR Principles. We address two challenges posed by growth in data size and complexity.

Molecular Graphics: Bridging Structural Biologists and Computer Scientists.

Visualization of molecular structures is one of the most common tasks carried out by structural biologists, typically using software, such as Chimera, COOT, PyMOL, or VMD. In this Perspective article, we outline how past developments in computer graphics and data visualization have expanded the understanding of biomolecular function, and we summarize recent advances that promise to further transform structural biology. We also highlight how progress in molecular graphics has been impeded by communication barriers between two communities: the computer scientists driving these advances, and the structural and computational biologists who stand to benefit.

Bringing Molecular Dynamics Simulation Data into View.

Molecular dynamics (MD) simulations monitor time-resolved motions of macromolecules. While visualization of MD trajectories allows an instant and intuitive understanding of dynamics and function, so far mainly static representations are provided in the published literature. Recent advances in browser technology may allow for the sharing of trajectories through interactive visualization on the web.

NGL viewer: web-based molecular graphics for large complexes.

Motivation: The interactive visualization of very large macromolecular complexes on the web is becoming a challenging problem as experimental techniques advance at an unprecedented rate and deliver structures of increasing size.

Results: We have tackled this problem by developing highly memory-efficient and scalable extensions for the NGL WebGL-based molecular viewer and by using Macromolecular Transmission Format (MMTF), a binary and compressed MMTF. These enable NGL to download and render molecular complexes with millions of atoms interactively on desktop computers and smartphones alike, making it a tool of choice for web-based molecular visualization in research and education.

FragFit: a web-application for interactive modeling of protein segments into cryo-EM density maps.

Cryo-electron microscopy (cryo-EM) is a standard method to determine the three-dimensional structures of molecular complexes. However, easy to use tools for modeling of protein segments into cryo-EM maps are sparse. Here, we present the FragFit web-application, a web server for interactive modeling of segments of up to 35 amino acids length into cryo-EM density maps.

The arrestin-1 finger loop interacts with two distinct conformations of active rhodopsin.

Signaling of the prototypical G protein-coupled receptor (GPCR) rhodopsin through its cognate G protein transducin (G) is quenched when arrestin binds to the activated receptor. Although the overall architecture of the rhodopsin/arrestin complex is known, many questions regarding its specificity remain unresolved. Here, using FTIR difference spectroscopy and a dual pH/peptide titration assay, we show that rhodopsin maintains certain flexibility upon binding the "finger loop" of visual arrestin (prepared as synthetic peptide ArrFL-1).

NGLview-interactive molecular graphics for Jupyter notebooks.

Summary: NGLview is a Jupyter/IPython widget to interactively view molecular structures as well as trajectories from molecular dynamics simulations. Fast and scalable molecular graphics are provided through the NGL Viewer. The widget supports showing data from the file-system, online data bases and from objects of many popular analysis libraries including mdanalysis, mdtraj, pytraj, rdkit and more.

A fragment based method for modeling of protein segments into cryo-EM density maps.

Background: Single-particle analysis of electron cryo-microscopy (cryo-EM) is a key technology for elucidation of macromolecular structures. Recent technical advances in hardware and software developments significantly enhanced the resolution of cryo-EM density maps and broadened the applicability and the circle of users. To facilitate modeling of macromolecules into cryo-EM density maps, fast and easy to use methods for modeling are now demanded.

MMTF-An efficient file format for the transmission, visualization, and analysis of macromolecular structures.

Recent advances in experimental techniques have led to a rapid growth in complexity, size, and number of macromolecular structures that are made available through the Protein Data Bank. This creates a challenge for macromolecular visualization and analysis. Macromolecular structure files, such as PDB or PDBx/mmCIF files can be slow to transfer, parse, and hard to incorporate into third-party software tools.

Towards an efficient compression of 3D coordinates of macromolecular structures.

The size and complexity of 3D macromolecular structures available in the Protein Data Bank is constantly growing. Current tools and file formats have reached limits of scalability. New compression approaches are required to support the visualization of large molecular complexes and enable new and scalable means for data analysis.

The RCSB protein data bank: integrative view of protein, gene and 3D structural information.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, http://rcsb.org), the US data center for the global PDB archive, makes PDB data freely available to all users, from structural biologists to computational biologists and beyond. New tools and resources have been added to the RCSB PDB web portal in support of a 'Structural View of Biology.

SL2: an interactive webtool for modeling of missing segments in proteins.

SuperLooper2 (SL2) (http://proteinformatics.charite.de/sl2) is the updated version of our previous web-server SuperLooper, a fragment based tool for the prediction and interactive placement of loop structures into globular and helical membrane proteins.

Role of Structural Dynamics at the Receptor G Protein Interface for Signal Transduction.

GPCRs catalyze GDP/GTP exchange in the α-subunit of heterotrimeric G proteins (Gαßγ) through displacement of the Gα C-terminal α5 helix, which directly connects the interface of the active receptor (R*) to the nucleotide binding pocket of G. Hydrogen-deuterium exchange mass spectrometry and kinetic analysis of R* catalysed G protein activation have suggested that displacement of α5 starts from an intermediate GDP bound complex (R*•GGDP). To elucidate the structural basis of receptor-catalysed displacement of α5, we modelled the structure of R*•GGDP.

NGL Viewer: a web application for molecular visualization.

The NGL Viewer (http://proteinformatics.charite.de/ngl) is a web application for the visualization of macromolecular structures.

Position of transmembrane helix 6 determines receptor G protein coupling specificity.

G protein coupled receptors (GPCRs) transmit extracellular signals into the cell by binding and activating different intracellular signaling proteins, such as G proteins (Gαβγ, families Gi, Gs, Gq, G12/13) or arrestins. To address the issue of Gs vs Gi coupling specificity, we carried out molecular dynamics simulations of lipid-embedded active β2-adrenoceptor (β2AR*) in complex with C-terminal peptides derived from the key interaction site of Gα (GαCT) as surrogate of Gαβγ. We find that GiαCT and GsαCT exploit distinct cytoplasmic receptor conformations that coexist in the uncomplexed β2AR*.

Precision vs flexibility in GPCR signaling.

The G protein coupled receptor (GPCR) rhodopsin activates the heterotrimeric G protein transducin (Gt) to transmit the light signal into retinal rod cells. The rhodopsin activity is virtually zero in the dark and jumps by more than one billion fold after photon capture. Such perfect switching implies both high fidelity and speed of rhodopsin/Gt coupling.

Voronoia4RNA--a database of atomic packing densities of RNA structures and their complexes.

Voronoia4RNA (http://proteinformatics.charite.de/voronoia4rna/) is a structural database storing precalculated atomic volumes, atomic packing densities (PDs) and coordinates of internal cavities for currently 1869 RNAs and RNA-protein complexes.