CapsidMaps: protein-protein interaction pattern discovery platform for the structural analysis of virus capsids using Google Maps

Abstract

Structural analysis and visualization of protein-protein interactions is a challenging task since it is difficult to appreciate easily the extent of all contacts made by the residues forming the interfaces. In the case of viruses, structural analysis becomes even more demanding because several interfaces coexist and, in most cases, these are formed by hundreds of contacting residues that belong to multiple interacting coat proteins. CapsidMaps is an interactive analysis and visualization tool that is designed to benefit the structural virology community. Developed as an improved extension of the φ-ψ Explorer, here we describe the details of its design and implementation. We present results of analysis of a spherical virus to showcase the features and utility of the new tool. CapsidMaps also facilitates the comparison of quaternary interactions between two spherical virus particles by computing a similarity (S)-score. The tool can also be used to identify residues that are solvent exposed and in the process of locating antigenic epitope regions as well as residues forming the inside surface of the capsid that interact with the nucleic acid genome. CapsidMaps is part of the VIPERdb Science Gateway, and is freely available as a web-based and cross-browser compliant application at http://viperdb.scripps.edu.

Keywords: Heat maps; Quaternary interactions; Similarity score; Viral capsids; Web interface.

Figure 1

Schematic representation of T=1, T=3, and T=4 icosahedral lattices. Each trapezoid corresponds to an independent subunit. In the case of T=1 capsids, all the subunits occupy an equivalent environment, namely A, whereas in T>1 capsids, subunits occupy three, four or more distinct environments (in this case A, B, C, or D). The central icosahedral asymmetric unit is highlighted in each case. Adapted from Reddy et al..

Figure 2

Coordinate system transformation and polar azimuthal orthographic projection of the center of mass of a protein residue. Every coat protein residue is represented as a point in space (black dots). Cartesian coordinates (x, y, z) are transformed into an spherical system (r, φ, ψ), setting, leaving all residues lying on the surface of a unit sphere. An orthogonal projection (parallel to the Z axis) onto a tangential plane through the north pole is then applied, ending up with a two dimensional φ-ψ polar map representation of the relative position of all coat protein residues.

Figure 3

The CapsidMaps tool integrates several layers. The VIPER data base is at the foundation of the platform. The client layer communicates with the server layer to extract specific information from the data base. The client then displays the data dynamically using the Google Maps libraries.

Figure 4

Black Beetle Virus spherical capsid (PDBID=2bbv, T=3). (Top left) Full capsid structure formed by 180 independent coat protein subunits, color coded according to their specific environment using a standard scheme; A in blue, B in red and C in green. The central icosahedral asymmetric unit (CIAU) is highlighted by a white triangle, showing where the North Pole would be in the unit sphere by a yellow dot. In this representation the positive X axis points right, and the positive Y axis points up. (Top right and Clockwise) Polar φ-ψ maps of the CIAU (represented by a triangular black frame), showing different regions of the coat proteins: Core, Interface and Solvent exposed. Symbols are colored according to the subunit they belong to.

Figure 5

Black Beetle Virus heat-maps, color coded according to the local residue density; areas of higher density are colored red and areas of lower density appear green. (Top left) Control panel with options selected to hide all subunits and the CIAU, leaving the heat-map layer on. (Top right and Clockwise) φ-ψ heat-maps showing different regions of the coat proteins: Core, Interface and Solvent exposed.

Figure 6

Black Beetle Virus Interface residues, color coded according to four different criteria: (Top left and Clockwise) Capsid environment type, Family sequence conservation, Number of interaction contacts per residue, and Solvent accessible surface area. When clicking on a particular marker, a balloon shows general information about the corresponding residue, and hovering over it shows a synthesis of the data.

Figure 7

Black Beetle Virus interface residues, color coded according to the local subunit environment. (Left) The application has the ability to calculate the S-score between two capsids. Once a second virus is selected by its PDBID, the metrics value is displayed in the control panel. Additionally, residues of the second virus are also displayed on the map (gray color), allowing for the visual assessment of where main quaternary differences might be. (Right) Another added feature is the ability to search for a specific residue by specifying a subunit and a sequence id.