PrankWeb is a web-based application that allows to predict and visualize protein-ligand binding sites. Furthermore, it allows to compare the location of predicted pockets with highly conserved areas as well as actual ligand binding sites. All one needs to use PrankWeb is a device with a web-browser that supports WebGL.
There are two options to analyze a protein. A protein PDB file can be uploaded from user's computer, or PrankWeb can download it automatically from PDB database provided the protein identification code.
Besides selecting what protein to analyze, one can also specify whether evolutionary conservation should be included in the prediction model by checking the "Run conservation analysis" checkbox. PrankWeb contains two pretrained models for pocket prediction. Note that calculating conservation score for user-defined protein file can significantly increase the time of analysis unless you specify its PDB identification code or upload multiple sequence alignments for homology calculation.
There are three ways how to calculate the conservation score for the protein.
Once the protein visualization is loaded, three main panels appear: sequence visualization, structural visualization and the pocket panel.
The largest panel contains the three-dimensional visualization of the protein.
The molecule can be rotated by moving mouse while holding left mouse button. On a touch device, just slide your finger. To zoom in or out, move your mouse while holding the right mouse button or use the pinch gesture on a touch display. In order to move the protein, do the same, but this time hold the wheel button. Lastly, for slabbing the protein, scroll the mouse wheel or use the three finger gesture.
Using the buttons in the top-right corner, one can:
Display a help window.
Setup the scene such as the visualization background or the field of view.
Create a snapshot of current visualization.
Toggle advanced control panels.
Toggle full-screen mode.
By toggling the advanced control panel, one has full control over the content of the visualization. First, select what part of visualization to edit in the tree control on the left, then edit its properties or create new nodes using the right panel. For example, to increase the surface probe radius, click on the surface section on the left (subsection of polymer). Now, in the update visual section, expand the visual type section and use the probe radius trackbar to update the value. Please be cautious, because as of May 2017, LiteMol does not support Undo operation. It will be added soon, though. For more help with LiteMol, please visit its wiki page.3
LiteMol visualization possibilities are very powerful. The visualization from figure above was achived by hiding the default protein surface and creating a small surface for the individual pockets.
The panel above protein 3D visualization displays protein sequence.
As one hovers over the sequence with mouse, the residues are highlighted in the 3D visualization. This feature allows to analyze the protein both from the structural and sequential point of view. By default, the sequence view is zoomed out so that the whole protein is displayed. You can use the trackbar control to zoom in, or select the area with mouse and zoom to the selection. A snapshot of the sequence can be captured and exported to SVG (Scalable Vector Graphics) file using the rightmost button.
The right panel contains several control buttons and a list of predicted pockets. Use the control buttons to download PrankWeb report, share the website, hide the sequence view or switch between the structural views. PrankWeb report is a ZIP package containing all following files:
Original pdb file uploaded, or the protein file downloaded from RCSB PDB.
Prediction JSON file containing a list of pockets, their scores and their location i.e. a list of atoms and residues forming the pocket. (Output of P2Rank)
PyMol script for offline visualization. (Output of P2Rank).
Conservation scores for each residue of the protein calculated using JSD method (see the original thesis for more details). The file is in TSV (Tab Separated Values) format. First column identifies the index, second contains the score and the last column contains the residues from multiple sequence alignment. The first characters in the last column are the residues of the analyzed protein file.
Multiple sequence alignments in FASTA format that were used to calculate conservation score.
In the pocket list, pocket name, rank, size and average conservation score (if available) is displayed for each pocket. Moreover, one can highlight the pocket is the 3D visualization by hovering button. After clicking that button, the camera will zoom in to the pocket. By clicking the button, one can toggle the pocket visibility in both structural and sequence visualizations.
For more technical details of this project, please see the original thesis document.