Caver Web 1.0: identification of tunnels and channels in proteins and analysis of ligand transport

Abstract

Caver Web 1.0 is a web server for comprehensive analysis of protein tunnels and channels, and study of the ligands' transport through these transport pathways. Caver Web is the first interactive tool allowing both the analyses within a single graphical user interface. The server is built on top of the abundantly used tunnel detection tool Caver 3.02 and CaverDock 1.0 enabling the study of the ligand transport. The program is easy-to-use as the only required inputs are a protein structure for a tunnel identification and a list of ligands for the transport analysis. The automated guidance procedures assist the users to set up the calculation in a way to obtain biologically relevant results. The identified tunnels, their properties, energy profiles and trajectories for ligands' passages can be calculated and visualized. The tool is very fast (2-20 min per job) and is applicable even for virtual screening purposes. Its simple setup and comprehensive graphical user interface make the tool accessible for a broad scientific community. The server is freely available at https://loschmidt.chemi.muni.cz/caverweb.

Figure 1.

Workflow diagram of Caver Web 1.0. The process consists of four phases: (1) structure pre-treatment, (2) detection of the starting point, (3) identification of tunnels/channels and (4) analysis of ligand transport. *Ligand structures can be uploaded in all formats supported by Open Babel (http://openbabel.org/docs/current/FileFormats/Overview.html).

Figure 2.

The graphical user interface of the Caver Web 1.0. The figure presents inputs and outputs obtained for the enzyme haloalkane dehalogenase LinB (PDB ID: 1CV2). (A) The ‘Select structure’ panel shows detected biological units for the provided protein structure. (B) The ‘Starting point’ panel for tunnel detection can be selected using four different methods. (C) The ‘Tunnel info’ panel provides an overview of the detected tunnels. (D) The ‘Tunnel details’ pop-up window presents detailed information about the selected tunnel. (E) The ‘Tunnel profile’ pop-up window shows the radius profile of the selected tunnels. (F) The ‘New CaverDock calculation’ pop-up window allows users to perform ligand transport analyses. (G) The ‘CaverDock results’ pop-up window displays calculated energy profiles for the selected ligand.