I have modelled phosphocarrier protein HPr of a gram positive pathogen (87 aa length). I want to perform an automated virtual screening for this model against a set of small molecules. The DrugBank database (@ http://www.drugbank.ca/molecules/5689) says Phosphonoserine is a drug against the HPr protein which has been proved experimentally. Now I want to perform an automated virtual screening for the modeled protein against all the available phosphonoserine like small molecules which are accessible via publically available databases like PubChem (PubChem just has 26 phosphonoserine like molecules filtered after Lipinski rule of 5, and I want to increse the number of ligand dataset). It would be better if the complete process is automated. I can run AutoDock 4.2 independently along with the virtual screening software PyRx.
My concern is with obtaining a set of small molecules which would obey drug likeliness parameters and converting it to a PDB file format, so that it can be submitted to PyRx. OR can the complete process be automated in order to obtain the end results ?
But dear Quintino, I am not an efficient programmer. so are there any readily serviceable open-source tools existing ?
The docking is one thing, AutoDock Vina is free to use.
But you also need to pre-process the input structures (to get rid of non-druglike compounds) and post-process the output data to pick the best structures.
You will probably find the free chemoinformatic tools (CDK or RDKit) available for KNIME useful in this regard (http://www.knime.org/ - KNIME is also free). these can calculate and filter on chemical and other properties and translate between file formats. KNIME is just great for the non-programmers amongst us
An additional point, and advise to all virtual screeners - always use as your last step in selection of compounds to screen, that not to be underated piece of hardware, the chemically knowledgeable human brain!
Dear Mr. Telkar,
You can use AUDocker LE: A GUI for virtual screening with AUTODOCK Vina (http://link.springer.com/article/10.1186%2F1756-0500-4-445). It will help you to do automated virtual screening of any database against a protein of your interest.
Another option is to use PyRx (http://pyrx.sourceforge.net/). PyRx is a virtual screening software that can be used to screen libraries of compounds against potential drug targets. This program can be run from any platform and helps users in every step of this process - from data preparation to job submission and analysis of the results.
I hope these suggestions help you in accomplishing your work.
All the best!
Kuldeep
Filtering the dataset for druglike compounds and eliminating undesirable structural features is an important step in virtual screening. As John pointed out KNIME and RDkit are open source tools available for non-programmers.
Raccoon is also a GUI that automates, amongst other things, preparation of ligand files either in PDB, MOL2 or PDBQT format for virtual screening using Autodock. (http://autodock.scripps.edu/resources/raccoon).
Once the ligand structures are in PDB format, virtual screening using PyRX is not a problem.
You can use openbabel to convert ligand to PDB format.
There are many drugs which flunk the lipinski's rule, so you can consider even more ligands. I prefer Vina first for Virtual screening followed by AutoDock4 for details interaction study.
Guilherme Oliveira Quintino
To run the script, one needs to obtain .pdbqt files of ligands. Is there a way to do this for e.g. 500-600 compounds fast and efficiently?
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