We are going to specifically block interaction between two proteins with a possible therapeutic approach. We are working on synthetic peptides and in silico screened chemical compounds. Can anyone help which method is better or discuss other alternatives? Any discussion would be appreciated.
First you need to know which residues of each protein are involved in protein-protein interaction. Next you can find a binding site near that residues and finally you should find an appropriate target to destroy the participating residues in one of those proteins.
No single specific method can be suggested. First identify the small ligand molecules having binding affinity for your protein. If the interacting proteins are enzymes, at least one of these, a substrate, it's analogue or a pseudosubstrate may avoid protein-protein interaction!
It is usually considered to be very challenging to find compounds that inhibit protein-protein interactions. The reason for this is that such interaction often occur over a broad, flat surface with many contributing interactions. To increase the chance of success, look in the structure of the complex for a "hotspot," which is a small pocket that is a major determinant for the interaction. This should be the target.
If you start with a peptide, you should keep in mind that peptides have some disadvantages. For example, they usually are not bioavailable, so they have to be injected, and peptides made of the normal 20 amino acids found in proteins are subject to degradation by proteolysis. An effort will likely be needed to change the peptide to make it more "drug-like."
HI , please read this paper :
AnchorQuery: Rapid online virtual screening for small‐molecule protein‐protein interaction inhibitors.
- Badges
- Science topic
- Similar topics
- Biological Science
- Biochemistry
- Biomolecules
- Peptides