How to find the active site(s) in a drug target enzyme for molecular docking?
I want to predict possible or confirmed active sites in the following enzymes
Adenylosuccinate lyase PDB (4MX2)
N- myrsitoyl transferase PDB (2WUU)
You can pdbsum to find the active site of the protein/enzyme. The following link directs you to a tool called pdbsum. This website gives you something called lig-plot which illustrates the ligand with which the protein has been crystallized) bound to the active site. You just need to plug in the pdb id. You can make a note of the amino acids present in the active site and target them during docking. Hope this helps.
http://www.ebi.ac.uk/pdbsum/
http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=4mx2&template=ligands.html&l=1.1
Hi Arushdeep,
There are several tools available that can predict the catalytic residues in 3-D structures deposited in PDB. The most commonly used tool is "catalytic site atlas" and is available at http://www.ebi.ac.uk/thornton-srv/databases/CSA/ ( you can find the primary citation for this server at http://www.ncbi.nlm.nih.gov/pubmed/14681376). Another useful server is COFACTOR that does structure-based prediction of catalytic residues and it is from the Zhang Lab available at http://zhanglab.ccmb.med.umich.edu/COFACTOR/help.html (the primary citation for this server can be found at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394312/). As regards to prediction of well-characterized enzymes like adenylosuccinate lyase, their active sites are well documented and can be easily determined. To begin with, you can refer to my publication:
https://www.researchgate.net/publication/23708308_Elucidation_of_the_substrate_specificity_kinetic_and_catalytic_mechanism_of_adenylosuccinate_lyase_from_Plasmodium_falciparum
Article Elucidation of the substrate specificity, kinetic and cataly...
You may also try CASTp server available at http://sts.bioe.uic.edu/castp/
You may also try discovery studio visualizer it will also give you the co-ordinates of the active site which will be important for setting up docking parameter file. Hope this helps
Regards
Well, aside from using the database and binding site finder tool above I'd like to suggest you to search the site-directed mutagenesis study result. You can link the ligand-protein interaction data with the SDM study result to see if they are related to certain cavity, which is possibly a putative binding site.
Hope that help,
Radif
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