Versatile annotation and publication quality visualization of protein complexes using POLYVIEW-3D

Abstract

Background: Macromolecular visualization as well as automated structural and functional annotation tools play an increasingly important role in the post-genomic era, contributing significantly towards the understanding of molecular systems and processes. For example, three dimensional (3D) models help in exploring protein active sites and functional hot spots that can be targeted in drug design. Automated annotation and visualization pipelines can also reveal other functionally important attributes of macromolecules. These goals are dependent on the availability of advanced tools that integrate better the existing databases, annotation servers and other resources with state-of-the-art rendering programs.

Results: We present a new tool for protein structure analysis, with the focus on annotation and visualization of protein complexes, which is an extension of our previously developed POLYVIEW web server. By integrating the web technology with state-of-the-art software for macromolecular visualization, such as the PyMol program, POLYVIEW-3D enables combining versatile structural and functional annotations with a simple web-based interface for creating publication quality structure rendering, as well as animated images for Powerpoint, web sites and other electronic resources. The service is platform independent and no plug-ins are required. Several examples of how POLYVIEW-3D can be used for structural and functional analysis in the context of protein-protein interactions are presented to illustrate the available annotation options.

Conclusion: POLYVIEW-3D server features the PyMol image rendering that provides detailed and high quality presentation of macromolecular structures, with an easy to use web-based interface. POLYVIEW-3D also provides a wide array of options for automated structural and functional analysis of proteins and their complexes. Thus, the POLYVIEW-3D server may become an important resource for researches and educators in the fields of protein science and structural bioinformatics. The new server is available at http://polyview.cchmc.org/polyview3d.html.

Figure 1

An example of POLYVIEW-3D visualization of an inactive form of the regulatory domain of LicT antiterminator (see text for details). The overall structure of the regulatory dimer is shown, with one chain shown using the surface, and the other chain using the cartoon rendering, respectively. The residues found to be within interaction interface are shown in magenta and yellow.

Figure 2

Chain A of the regulatory domain of LicT protein shown alone, with two largest pockets on the surface that partially overlap with the interaction interface (shown in magenta), as identified using CASTp, highlighted in blue and cyan (the latter for residues within the pockets that are also involved in the formation of the interaction interface).

Figure 3

Chain A of the regulatory domain LicT protein shown alone, with surface exposed residues colored according to their evolutionary conservation, as assessed by the ConSurf server (residues that are highly conserved are shown in deep purple, whereas highly variable positions are shown in cyan).

Figure 4

Same as Figures 2 and 3, with colors representing B-factors this time (red corresponding to highly flexible, and white to relatively rigid parts of the structure, respectively), and with the semitransparent rendering of the surface (residues forming pockets shown in Figure 2 are highlighted using stick models for their side chains).

Figure 5

Application of POLYVIEW-3D to the analysis and further assessment (in terms of the overlap between predicted and observed interaction interfaces) of protein docking models, generated for LicT using the ClusPro server (see text for details). An overall view of the top scoring model is shown, with PRD1 domains forming a qualitatively correct dimer interface. The residues found to be within the interaction interface in this model, which are also predicted by SPPIDER as interaction sites, are highlighted in red, residues observed in the model within interacting sites and not predicted as such are shown in blue, and residues predicted to be interacting sites but not involved in interactions in the model of the complex are shown in yellow, respectively.

Figure 6

Visualization of an alternative (and qualitatively incorrect) ClusPro model for the LicT regulatory domain complex, using the same color scheme as in Figure 5. Note the lack of overlap with SPPIDER predictions in this case.