UCSF ChimeraX is the next‐generation interactive visualization program from the Resource for Biocomputing, Visualization, and Informatics (RBVI), following UCSF Chimera. ChimeraX brings (a) ...significant performance and graphics enhancements; (b) new implementations of Chimera's most highly used tools, many with further improvements; (c) several entirely new analysis features; (d) support for new areas such as virtual reality, light‐sheet microscopy, and medical imaging data; (e) major ease‐of‐use advances, including toolbars with icons to perform actions with a single click, basic “undo” capabilities, and more logical and consistent commands; and (f) an app store for researchers to contribute new tools. ChimeraX includes full user documentation and is free for noncommercial use, with downloads available for Windows, Linux, and macOS from https://www.rbvi.ucsf.edu/chimerax.
UCSF ChimeraX is next‐generation software for the visualization and analysis of molecular structures, density maps, 3D microscopy, and associated data. It addresses challenges in the size, scope, and ...disparate types of data attendant with cutting‐edge experimental methods, while providing advanced options for high‐quality rendering (interactive ambient occlusion, reliable molecular surface calculations, etc.) and professional approaches to software design and distribution. This article highlights some specific advances in the areas of visualization and usability, performance, and extensibility. ChimeraX is free for noncommercial use and is available from http://www.rbvi.ucsf.edu/chimerax/ for Windows, Mac, and Linux.
Advances in computational tools for atomic model building are leading to accurate models of large molecular assemblies seen in electron microscopy, often at challenging resolutions of 3–4 Å. We ...describe new methods in the UCSF ChimeraX molecular modeling package that take advantage of machine‐learning structure predictions, provide likelihood‐based fitting in maps, and compute per‐residue scores to identify modeling errors. Additional model‐building tools assist analysis of mutations, post‐translational modifications, and interactions with ligands. We present the latest ChimeraX model‐building capabilities, including several community‐developed extensions. ChimeraX is available free of charge for noncommercial use at https://www.rbvi.ucsf.edu/chimerax.
In the post-genomic era, the rapid increase in high-throughput data calls for computational tools capable of integrating data of diverse types and facilitating recognition of biologically meaningful ...patterns within them. For example, protein-protein interaction data sets have been clustered to identify stable complexes, but scientists lack easily accessible tools to facilitate combined analyses of multiple data sets from different types of experiments. Here we present clusterMaker, a Cytoscape plugin that implements several clustering algorithms and provides network, dendrogram, and heat map views of the results. The Cytoscape network is linked to all of the other views, so that a selection in one is immediately reflected in the others. clusterMaker is the first Cytoscape plugin to implement such a wide variety of clustering algorithms and visualizations, including the only implementations of hierarchical clustering, dendrogram plus heat map visualization (tree view), k-means, k-medoid, SCPS, AutoSOME, and native (Java) MCL.
Results are presented in the form of three scenarios of use: analysis of protein expression data using a recently published mouse interactome and a mouse microarray data set of nearly one hundred diverse cell/tissue types; the identification of protein complexes in the yeast Saccharomyces cerevisiae; and the cluster analysis of the vicinal oxygen chelate (VOC) enzyme superfamily. For scenario one, we explore functionally enriched mouse interactomes specific to particular cellular phenotypes and apply fuzzy clustering. For scenario two, we explore the prefoldin complex in detail using both physical and genetic interaction clusters. For scenario three, we explore the possible annotation of a protein as a methylmalonyl-CoA epimerase within the VOC superfamily. Cytoscape session files for all three scenarios are provided in the Additional Files section.
The Cytoscape plugin clusterMaker provides a number of clustering algorithms and visualizations that can be used independently or in combination for analysis and visualization of biological data sets, and for confirming or generating hypotheses about biological function. Several of these visualizations and algorithms are only available to Cytoscape users through the clusterMaker plugin. clusterMaker is available via the Cytoscape plugin manager.
The dramatic increase in heterogeneous types of biological data--in particular, the abundance of new protein sequences--requires fast and user-friendly methods for organizing this information in a ...way that enables functional inference. The most widely used strategy to link sequence or structure to function, homology-based function prediction, relies on the fundamental assumption that sequence or structural similarity implies functional similarity. New tools that extend this approach are still urgently needed to associate sequence data with biological information in ways that accommodate the real complexity of the problem, while being accessible to experimental as well as computational biologists. To address this, we have examined the application of sequence similarity networks for visualizing functional trends across protein superfamilies from the context of sequence similarity. Using three large groups of homologous proteins of varying types of structural and functional diversity--GPCRs and kinases from humans, and the crotonase superfamily of enzymes--we show that overlaying networks with orthogonal information is a powerful approach for observing functional themes and revealing outliers. In comparison to other primary methods, networks provide both a good representation of group-wise sequence similarity relationships and a strong visual and quantitative correlation with phylogenetic trees, while enabling analysis and visualization of much larger sets of sequences than trees or multiple sequence alignments can easily accommodate. We also define important limitations and caveats in the application of these networks. As a broadly accessible and effective tool for the exploration of protein superfamilies, sequence similarity networks show great potential for generating testable hypotheses about protein structure-function relationships.
Molecular Visualization on the Holodeck Goddard, Thomas D.; Brilliant, Alan A.; Skillman, Thomas L. ...
Journal of Molecular Biology/Journal of molecular biology,
10/2018, Letnik:
430, Številka:
21
Journal Article
Recenzirano
Odprti dostop
Can virtual reality be useful for visualizing and analyzing molecular structures and three-dimensional (3D) microscopy? Uses we are exploring include studies of drug binding to proteins and the ...effects of mutations, building accurate atomic models in electron microscopy and x-ray density maps, understanding how immune system cells move using 3D light microscopy, and teaching schoolchildren about biomolecules that are the machinery of life. Virtual reality (VR) offers immersive display with a wide field of view and head tracking for better perception of molecular architectures and uses 6-degree-of-freedom hand controllers for simple manipulation of 3D data. Conventional computer displays with trackpad, mouse and keyboard excel at two-dimensional tasks such as writing and studying research literature, uses for which VR technology is at present far inferior. Adding VR to the conventional computing environment could improve 3D capabilities if new user-interface problems can be solved. We have developed three VR applications: ChimeraX for analyzing molecular structures and electron and light microscopy data, AltPDB for collaborative discussions around atomic models, and Molecular Zoo for teaching young students characteristics of biomolecules. Investigations over three decades have produced an extensive literature evaluating the potential of VR in research and education. Consumer VR headsets are now affordable to researchers and educators, allowing direct tests of whether the technology is valuable in these areas. We survey here advantages and disadvantages of VR for molecular biology in the context of affordable and dramatically more powerful VR and graphics hardware than has been available in the past.
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•Are there compelling uses for virtual reality in molecular visualization?•VR allows clear views and analysis of time-varying atomic models and 3D microscopy.•Collaborative discussions benefit from room-scale virtual protein models.•Handling dynamic biomolecules can inspire young students to study science.•We give examples and identify key problems in using VR for scientific visualization.
Structural modeling of macromolecular complexes greatly benefits from interactive visualization capabilities. Here we present the integration of several modeling tools into UCSF Chimera. These ...include comparative modeling by MODELLER, simultaneous fitting of multiple components into electron microscopy density maps by IMP MultiFit, computing of small-angle X-ray scattering profiles and fitting of the corresponding experimental profile by IMP FoXS, and assessment of amino acid sidechain conformations based on rotamer probabilities and local interactions by Chimera.
Leukocytes and other amoeboid cells change shape as they move, forming highly dynamic, actin-filled pseudopods. Although we understand much about the architecture and dynamics of thin lamellipodia ...made by slow-moving cells on flat surfaces, conventional light microscopy lacks the spatial and temporal resolution required to track complex pseudopods of cells moving in three dimensions. We therefore employed lattice light sheet microscopy to perform three-dimensional, time-lapse imaging of neutrophil-like HL-60 cells crawling through collagen matrices. To analyze three-dimensional pseudopods we: (i) developed fluorescent probe combinations that distinguish cortical actin from dynamic, pseudopod-forming actin networks, and (ii) adapted molecular visualization tools from structural biology to render and analyze complex cell surfaces. Surprisingly, three-dimensional pseudopods turn out to be composed of thin (<0.75 µm), flat sheets that sometimes interleave to form rosettes. Their laminar nature is not templated by an external surface, but likely reflects a linear arrangement of regulatory molecules. Although we find that Arp2/3-dependent pseudopods are dispensable for three-dimensional locomotion, their elimination dramatically decreases the frequency of cell turning, and pseudopod dynamics increase when cells change direction, highlighting the important role pseudopods play in pathfinding.
Comparing related structures and viewing the structures in the context of sequence alignments are important tasks in protein structure-function research. While many programs exist for individual ...aspects of such work, there is a need for interactive visualization tools that: (a) provide a deep integration of sequence and structure, far beyond mapping where a sequence region falls in the structure and vice versa; (b) facilitate changing data of one type based on the other (for example, using only sequence-conserved residues to match structures, or adjusting a sequence alignment based on spatial fit); (c) can be used with a researcher's own data, including arbitrary sequence alignments and annotations, closely or distantly related sets of proteins, etc.; and (d) interoperate with each other and with a full complement of molecular graphics features. We describe enhancements to UCSF Chimera to achieve these goals.
The molecular graphics program UCSF Chimera includes a suite of tools for interactive analyses of sequences and structures. Structures automatically associate with sequences in imported alignments, allowing many kinds of crosstalk. A novel method is provided to superimpose structures in the absence of a pre-existing sequence alignment. The method uses both sequence and secondary structure, and can match even structures with very low sequence identity. Another tool constructs structure-based sequence alignments from superpositions of two or more proteins. Chimera is designed to be extensible, and mechanisms for incorporating user-specific data without Chimera code development are also provided.
The tools described here apply to many problems involving comparison and analysis of protein structures and their sequences. Chimera includes complete documentation and is intended for use by a wide range of scientists, not just those in the computational disciplines. UCSF Chimera is free for non-commercial use and is available for Microsoft Windows, Apple Mac OS X, Linux, and other platforms from http://www.cgl.ucsf.edu/chimera.
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