I am working on one protein which is involved in cancer and some peptides were designed and used for the functional inhibition. I have performed molecular modeling and peptide interaction with that particular protein. Now I plan to design a ligand which can act better than the peptide and I want to further check in the wet lab. Can anyone advise how to design the small molecules based on their peptide interaction and inhibition? If possible please provide related literature articles which already have performed in this particular area.
How can I proceed to check the inhibition capability of the newly designed molecule using cell line assay?
You can use De novo design packages to help design your ligand. Alternatively, you can do it yourself by replacing certain groups/aminoacids in the peptide with some other groups that is complementary to the receptor and thus have better interactions/contacts. You can use combidock packages to attach various groups and dock them against the receptor. For wet lab experimants, it depends on which cell line assay you wish to use, there might already be protocols since you have mentioned that the initial peptides were designed for functional inhibition.
You can refer peptidomimetic based drug design approach which is well validated as protease inhibitors. Once you are done with it, you can design small molecule inhibitors for your protein of interest.
There are several literature available on the topic. It will be better if you search for it since you know what exactly you want.
To begin with, you can refer this article, "Design of lead peptide drugs from mushroom targeting cysteine proteases"
All the best.
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