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Comparative Study
. 2012:819:105-26.
doi: 10.1007/978-1-61779-465-0_8.

Virtual ligand screening against comparative protein structure models

Hao Fan  1 , John J Irwin, Andrej Sali
Affiliations
Comparative Study

Virtual ligand screening against comparative protein structure models

Hao Fan et al. Methods Mol Biol. 2012.

Abstract

Virtual ligand screening uses computation to discover new ligands of a protein by screening one or more of its structural models against a database of potential ligands. Comparative protein structure modeling extends the applicability of virtual screening beyond the atomic structures determined by X-ray crystallography or NMR spectroscopy. Here, we describe an integrated modeling and docking protocol, combining comparative modeling by MODELLER and virtual ligand screening by DOCK.

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Figures

Figure 1
Figure 1
The automated modeling and docking pipeline. Numbers in parentheses indicate the corresponding section in the text.
Figure 2
Figure 2
File “ADA.ali” in the “PIR” format. This file specifies the target sequence. See the MODELLER manual for the detailed description of the format.
Figure 3
Figure 3
File “search_templates.py”. This script searches for potential template structures in a database of non-redundant PDB sequences.
Figure 4
Figure 4
File “align.ali” in the “PIR” format. The file specifies the alignment between the sequences of ADA and 2AMX (A chain).
Figure 5
Figure 5
File “build_model.py”. The script generates 500 models of ADA based on 2AMX with “automodel” routine.
Figure 6
Figure 6
File “loop_model.py”. Input script file that generates 2500 models with the “loopmodel” routine.
Figure 7
Figure 7
A section of file “INDOCK” containing some input parameters for DOCK 3.5.54.
Figure 8
Figure 8
A section of file “OUTDOCK” containing docking scores of two DUD molecules.
Figure 9
Figure 9
The enrichment curve for virtual screening of the DUD database against the ADA model based on 2AMX. The ligand enrichment is quantified by the logAUC of 40.3.
Figure 10
Figure 10
Schematic description of the automated preparation of receptor binding site, including sphere and scoring grids generation.
Figure 11
Figure 11
(A) The matching spheres (dark grey) and DelPhi spheres (light grey) generated for the binding site of the ADA model (cartoon) based on 2AMX. (B) The docking pose (stick) and the 2D structure of one ADA ligand – 1-deazaadenosine (PubChem ID: 159738, ZINC ID: C03814313) – as well as the matching spheres (light grey)
See this image and copyright information in PMC

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