iDrug: a web-accessible and interactive drug discovery and design platform

Abstract

Background: The progress in computer-aided drug design (CADD) approaches over the past decades accelerated the early-stage pharmaceutical research. Many powerful standalone tools for CADD have been developed in academia. As programs are developed by various research groups, a consistent user-friendly online graphical working environment, combining computational techniques such as pharmacophore mapping, similarity calculation, scoring, and target identification is needed.

Results: We presented a versatile, user-friendly, and efficient online tool for computer-aided drug design based on pharmacophore and 3D molecular similarity searching. The web interface enables binding sites detection, virtual screening hits identification, and drug targets prediction in an interactive manner through a seamless interface to all adapted packages (e.g., Cavity, PocketV.2, PharmMapper, SHAFTS). Several commercially available compound databases for hit identification and a well-annotated pharmacophore database for drug targets prediction were integrated in iDrug as well. The web interface provides tools for real-time molecular building/editing, converting, displaying, and analyzing. All the customized configurations of the functional modules can be accessed through featured session files provided, which can be saved to the local disk and uploaded to resume or update the history work.

Conclusions: iDrug is easy to use, and provides a novel, fast and reliable tool for conducting drug design experiments. By using iDrug, various molecular design processing tasks can be submitted and visualized simply in one browser without installing locally any standalone modeling softwares. iDrug is accessible free of charge at http://lilab.ecust.edu.cn/idrug.

Keywords: 3D similarity calculation; Cavity detection; Online drug design platform; Pharmacophore search; Target prediction.

Figure 1

Workflow of iDrug automating pharmacophore modeling using Cavity and Pocket v.2, screening with PharmMapper and SHAFTS, and searching conformers using Cyndi. Common modules in iDrug platform are framed in black.

Figure 2

The iDrug interface. The task management is in the upper left and provides easy access to the full set of the history work. The Jmol-based molecular viewer is in the middle and displays the query molecule and results structure. The query editor is shown in the bottom and supports the interactive modification of the parameters based on the properties of the computational software. The results browser is on the right and displays the complete results along with the available details. In this figure, potential targets of tamoxifen obtained from iDrug are shown as well as the target pharmacophore model. On mouse over, a preview of the annotation information is displayed in a pop-up window, as shown for 2GPU in this example.

Figure 3

Pharmacophore depiction as used in this study on top of PDB entry: 1AQ1 (note that 1AQ1 with its cocrystallized ligand is used as a reference).