Application talk
Abstract
With recent advances in electron microscopy and other structure determination techniques, there has been a rapid increase in the complexity and size of biomacromolecular structures studied using structure determination techniques. This is reflected in the increase in the number of large structures (such as e.g. macromolecular machines) deposited to the Protein Data Bank (PDB) and Electron Microscopy Data Bank (EMDB). The PDB currently has 381 large complexes with more than 100K atoms and about 12% of PDB entries contain atomic coordinates for more than 10K atoms. One of the challenges facing the life-science community is to provide interactive visualisation of structural data and present the analysis over the web platforms used by the wider user community. Recent changes to web technologies has meant that highly-used technologies such as Java applets to provide interactive 3D visualisation are no longer available. There are many on-going efforts to develop an interactive 3D visualisation platform compatible with modern web frameworks, i.e. HTML5, and able to show large macromolecular structures. We address the challenges of delivering the 3D structural data and visualising the 3D structure without significant lag to enhance the user experience. This challenge has several aspects: first, the visualization of large structures is very time- and resource-demanding, therefore most current applications such as Jmol/JSMol that provide a web-based interactive viewer or PyMol, VMD and Chimera applications do not seem to be able to process the large structures or are very slow, losing the interactivity of the visualisation. Additionally, the bandwidth requirement to deliver such a large amount of data to the user presents a formidable challenge at this time. Addressing these challenges will enable data resources to make these data accessible in a web browser and provide the necessary interactivity to make the structure visualisation usable. We would like to present a solution of these issues at the application track. We have developed the web application LiteMol (http://webchemdev.ncbr.muni.cz/LiteMol/) – an interactive 3D viewer that is HTML5-compatible and able to quickly visualize even the largest structures such as the HIV capsid (PDB entry 3j3q), Panicum Mosaic virus (PDB entry 4v99) or ribosome 70s complex (PDB entry 4v4g). LiteMol contains not only standard visualization modes (ball and stick, surface, cartoon) but it can also show cryo-EM data and depict key information about the structures (e.g., electron density maps, ligand interactions, validation data, sequence annotations etc.). In parallel, we have developed a Coordinate Server (https://www.ebi.ac.uk/pdbe/coordinates/), which can select and provide only the relevant part of the structure, for example C alpha backbone, ligands, active sites etc. A combination of LiteMol and the Coordinate Server enables us to markedly shorten the time required for structure delivery and visualization in a web application. A first successful application of LiteMol and the Coordinate Server is currently incorporated in a development version of Protein Data Bank Europe’s webpages, where it enables 3D structures (see an example for the Zika virus here: http://wwwdev.ebi.ac.uk/pdbe/entry/pdb/5ire/protein/1 or change the PDB ID for other structures) or binding sites to be quickly shown (e.g. http://wwwdev.ebi.ac.uk/pdbe/entry/pdb/1cbs/bound/REA).
Authors
David Sehnal, CEITEC – Central European Institute of Technology, Masaryk University, and National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Czech Republic
Radka Svobodová Vařeková, CEITEC – Central European Institute of Technology, Masaryk University, and National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Czech Republic
Karel Berka, Department of Physical Chemistry, RCPTM, Faculty of Science, Palacký University, Czech Republic
Sameer Velankar, Protein Data Bank in Europe, EMBL-EBI, United Kingdom
Mandar Deshpande, Protein Data Bank in Europe, EMBL-EBI, United Kingdom
Lukáš Pravda, CEITEC – Central European Institute of Technology, Masaryk University, and National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Czech Republic
Jaroslav Koča, CEITEC – Central European Institute of Technology, Masaryk University, and National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Czech Republic