I have performed molecular docking and in the interaction diagram of the protein-phytochemical complex, only hydrophobic bonds are there, no hydrogen bonds are involved with any residues of the protein.
I had selected this one as one of the final compound after virtual screening. That compound behaved well in MD simulation considering low RMSD, RMSF values. Binding affinity was also higher than the control drug.
Now can I propose that compound as my potential findings for the paper??
Please help. Thanks a lot.
Yes, why not?
If the molecule binds to a hydrophobic pocket of the protein, a binding site that mostly contains hydrophobic amino acids and itself is a hydrophobic molecule: yes, definitely!
There might be no h-bond donor/acceptor or charged species present/accessible.
It's true, many publications with docking models mainly focus on hydrogen bond interactions, salt bridges,... The strength of a single hydrogen bond (or salt bridge) is much higher than that of a hydrophobic contact (this is the reason to focus on them). But the number of hydrophobic contacts prevails. So actually, the hydrophobic interactions are the most frequently observed ones. They are the hidden main player in protein-ligand interactions!
This might be interesting to read: Article A systematic analysis of atomic protein–ligand interactions in the PDB
The main problem with ligands that only interact through hydrophobic contacts is that these tend to show very low specificity - you may want to look at the possibility to introduce more specific interaction in further development of the lead. While hydrophobic interactions provide the majority of the interaction energy, hydrogen bonds and charge interactions provide specificity, reducing cross-reactivity with other hydrophobic binding pockets.
Yes, Annemarie Honegger is right! The specificity might be a problem. Sorry for not mentioning specificity, Sheikh Sunzid Ahmed!
But what about pi-pi stacking interactions (or amide-pi stacking, cationic-pi stacking), they are also hydrophobic (the aromatic ring might be part of the ligand), but more specific?
Bettina Lier No problem dear, thank you and thanks to Dear Annemarie Honegger for helping me to understand the specificity issue.
Yes, it's good as medicinal chemist but challenge inpharmacpkinetic point.
If it's lipophillic nature it's not good absorption in intestine and maybe also in stomach simultaneously, chance of more toxicity. Thus, oral design problem but may be solution also possible after know the complete detail about molecule and it's pharmaclogical activity.
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