VSpipe-GUI, an Interactive Graphical User Interface for Virtual Screening and Hit Selection

Abstract

Virtual screening of large chemical libraries is essential to support computer-aided drug development, providing a rapid and low-cost approach for further experimental validation. However, existing computational packages are often for specialised users or platform limited. Previously, we developed VSpipe, an open-source semi-automated pipeline for structure-based virtual screening. We have now improved and expanded the initial command-line version into an interactive graphical user interface: VSpipe-GUI, a cross-platform open-source Python toolkit functional in various operating systems (e.g., Linux distributions, Windows, and Mac OS X). The new implementation is more user-friendly and accessible, and considerably faster than the previous version when AutoDock Vina is used for docking. Importantly, we have introduced a new compound selection module (i.e., spatial filtering) that allows filtering of docked compounds based on specified features at the target binding site. We have tested the new VSpipe-GUI on the Hepatitis C Virus NS3 (HCV NS3) protease as the target protein. The pocket-based and interaction-based modes of the spatial filtering module showed efficient and specific selection of ligands from the virtual screening that interact with the HCV NS3 catalytic serine 139.

Keywords: AutoDock; AutoDock Vina; VSpipe; VSpipe-GUI; chemoinformatics; docking; drug design; virtual screening.

Figure 1

Comparison between VSpipe-CLI and VSpipe-GUI. Blue squares represent the common steps between both versions. Features only available in VSpipe-CLI are represented by uncolored rhomboid shapes. Green rhomboid shapes represent modified/new features implemented in VSpipe-GUI.

Figure 2

Main interface of VSpipe-GUI where users can customise their virtual screening run.

Figure 3

Module options available for users. (a) Options for receptor preparation according to users’ needs, (b) options to use already minimized compound libraries provided by VSpipe-GUI, (c) options to process (and minimize, if not done already) compounds uploaded by users in a single batch file, (d) options to process ligand compounds input by users.

Figure 4

Main GUI windows showing the options that the user can select to summarise the results in the filtering step. (a) Options to filter docking results according to various ligand physic-chemical properties, and (b) options to constrain the pocket-based and interaction-based spatial filtering (3D).

Figure 5

Spatial-based filtering procedure showing the workflow of both pocket-based filtering and interaction-based filtering.

Figure 6

(a) General view of MK-5172 and allosteric binding sites in the NS3 protease. The Maybridge 500 fragment library and MK-5712 are docked against the NS3 protease crystal structure; catalytic S139 is highlighted in cyan. (b) MK-5712 is bound to the catalytic site of NS3 protease; the hydrogen bond between catalytic S139 (cyan) and the sulfonamide oxygen is shown with a yellow dashed line. (c) In total, 93 ligands identified by the pocket-based filtering option occupy the active site. Possible hydrogen bond (shown by the yellow dashes) was identified by the interaction-based filtering option between an oxygen of CC01309 and S139Hg.