What exactly is reverse docking and how it could be used in in-silico drug desgn approach?
Dear Danish, see also a paper from Didier Rognan’s group (Muller et al J. Med. Chem., 2006, 49, 6768-6778) which shows that, using GOLD and docking against several thousand druggable active sites, it is possible to correctly identify possible target proteins for an active molecule.
Hi Danish,
Reverse docking is useful in identification of novel drug targets to of given ligand. I will suggest you to read following articles.
http://www.biomedcentral.com/1471-2105/13/S17/S6
To overcome the limitation of target space easily accessible by reverse docking, you can use ligand-based "target fishing" followed by structure-based site evaluation. An example is:
1. Nettles, J. H.; Jenkins, J. L.; Bender, A.; Deng, Z.; Davies, J. W.; Glick, M. Bridging chemical and biological space: "target fishing" using 2D and 3D molecular descriptors. J Med Chem 2006, 49, 6802-10.
A related new paper of interest may be -
Facing the Challenges of Structure-Based Target Prediction by Inverse Virtual Screening J. Chem. Inf. Model., 2014, 54 (6), pp 1676–1686
DOI: 10.1021/ci500130e
http://pubs.acs.org/doi/abs/10.1021/jm060902w
Reverse docking might be of special interest for laboratories dealing with natural products. They in general have a relatively small number of ligands, which are very likely to hit some target, but no idea which one. Of course, a better option would be an experimental screen against a broad target panel (there are a few commercial providers of such services out there), but that might be expensive exercise (tens of thousands US dollars per compound for comprehensive panels). So, virtual screening of the target space may help to narrow down the options for experimental follow-up..
Traditional docking screens for potential interacting compounds against a target protein of interest while the reverse is true for reverse docking or inverse docking where potential interacting proteins against a compound of interest are screened. Reverse docking could thus be used for drug repositioning whereby an existing drug is used to treat another disease that it was not originally developed for. You might also be interested in the field of chemogenomics, which in a nutshell is where similar ligands interact with similar target proteins. Thus, azole drugs that are known to interact with one member of the CYP450 family are also likely to interact with another member and thus compounds that was once used to treat fungal infection could be repositioned to treat breast cancer (by inhibiting the aromatase enzyme which is a CYP19A1).
The latter example could be inferred from:
Lapins M, Worachartcheewan A, Spjuth O, Georgiev V, Prachayasittikul V, et al. (2013) A Unified Proteochemometric Model for Prediction of Inhibition of Cytochrome P450 Isoforms. PLoS ONE 8(6): e66566.
http://dx.doi.org/10.1371/journal.pone.0066566
Dear Danish, see also a paper from Didier Rognan’s group (Muller et al J. Med. Chem., 2006, 49, 6768-6778) which shows that, using GOLD and docking against several thousand druggable active sites, it is possible to correctly identify possible target proteins for an active molecule.
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