I am trying to dock a ligand with protein 6LZG. But, being a newcomer in this docking field, could not get the active sites of that protein. So, Can anyone provide me the active sites of 6LZG protein? It will be helpful for me.
The spike protein does not have a specific "active site" like an enzyme, which has a specific substrate binding site and catalytic residues. It has a binding site which allows it to bind to its receptor in the host cell, the angiotensin converting enzyme II (ACE2), . Such binding to the host cell triggers a vast conformational change inthe spike protein, allowing it to attack the host cell membrane and to trigger the fusion of the viral membrane to the host membrane. Which parts of the virus you want to target depends on the goal of your study: are you trying to affect the receptor binding to inhibit the interaction with the ACE receptor, or are you looking for compounds that will stabilise the pre-fusion conformation of the spike protein and thereby inhibit membrane fusion?
Article Distinct conformational states of SARS-CoV-2 spike protein
https://www.nature.com/articles/s41467-020-20401-y?utm_source=xmol&utm_medium=affiliate&utm_content=meta&utm_campaign=DDCN_1_GL01_metadata
https://www.nature.com/articles/s41598-018-34171-7
https://www.pnas.org/content/114/42/11157
Annemarie Honegger thank you madam for your reply. Actually I was trying to check a organic molecule whether it binds with the 6LZG protein or not. That's I needed the active sites of the protein as I thought it would be better to go for specific sites docking rather than blind docking.
Thank you.
Subhadeep Sen Have you succeeded in your project? It seems very interesting. I would do a blind docking first and then focus on the residues forming the interaction interface with the ACE2 receptor. Contact me on LinkedIn to discuss more.
Pratik Srivastava thank you for your reply. Actually I am very new in this field, just trying to do some docking study, I don't have any experiences in this field. Your suggestion will definitely help me.
Subhadeep Sen There is a very good nature protocol article for autodock and its various protocols. Its your best resource for beginning docking. Just search "autodock nature protocol" on pubmed.
https://www.linkedin.com/in/pratik-srivastava-886a626b/
For a Beginner's Project I would recommend a simpler system, e.g. the coronavirus 3C-like protease, which is a verified drug target. See https://www.rcsb.org/news?year=2020&article=5e74d55d2d410731e9944f52&feature=true for an overview of the different viral proteins for which structural information is available
Annemarie Honegger Thank you madam for your valuable suggestion. Would you like to suggest some PDB IDs of some specific proteins.
Taking the 3C-like protease as an example, the overview I cited lists structure 6LU7 as an example (complex with an inhibitor) . If you search the PDB with that sequence, you'll find both unliganded and complex structures, some of very high resolution.
Rather than going for blind docking, I would suggest using DogSiteScorer to have a Lil bit insight of into active residues to set your grid box accordingly. Then you can alter/place your grid box somewhere else to have the best possible interaction of your protein active sites with a ligand that you are trying to dock.
Good luck Subhadeep Sen
Mudassir Khan thank you for your suggestion, I did not use the DogSiteScorer before, but will definitely use this software.
- Badges
- Science topic
- Similar topics
- Phytochemistry
- Extracts