I have an enzyme which has three GTP binding sites (predicted). I have predicted structure of enzyme using I-Tasser and now want to design peptide inhibitors to block GTP binding site which can easily be synthesized and tested.
How familiar are you with drug design?
Knowing GTP binding sites, you should analyze them and develop a pharmacophore, which you use to screen the known compound database and found possible inhibitors. Then you modify these inhibitors, analyze rsynth and, if it 100%, synthesize.
Simple? I spent several years to learn this. :)
What do you think about using phage display if you want peptide inhibitors? And why do you want the peptide inhibitors or for what use ultimately? If you want a drug, then would you rather use a scaffold with drug like properties with which to add binding groups. Or do you want to add a GTP like binding entity to the peptide? You may want to use the structure to come up with some type of idea for an initial peptide inhibitor, and then use phage display to improve the potency.
Marcia, I want peptide inhibitors that mimic GTP structure and can more efficiently bind to GTP binding site of enzyme. Basically, I want to block the GTP site. Can you suggest a way to design peptides based on GTP structure.
Dear Anil Tomar,
you can try building a pharmacophore model on the basis of GTP structure and its binding modes in the active site of its receptor. Then you can mannually consider the features to design your own peptide mannually. This is just an idea/approach i thought of by reading your above query. You can refine it by adding some more ideas like simulation studies etc. BUT, before doing all this you first stabilize your GTP-protein complex to be sure that the predicted GTP binding site is good enough to further design inhibitors. For this you should run simulation cycle for around 15-30 ns.
Regards,
Nutan
SATPdb: a database of structurally annotated therepeutic peptides.
http://crdd.osdd.net/raghava/satpdb/
paper link
http://nar.oxfordjournals.org/content/early/2015/11/01/nar.gkv1114.full
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