With no background in biological science, I need help with docking 2 proteins together. This issue is with regards to SARS-CoV-2. The 2 proteins are Spike glycoprotein and membrane protein. What are the necessary rules / requirements to be followed before docking the 2 above proteins?
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asked Jul 25, 2020 at 6:32
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2 Answers
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The main requirement is to have structures files with good resolution. According to RSCB PDB documentation:
Resolution is a measure of the quality of the data that has been collected on the crystal containing the protein or nucleic acid.
The figure bellow is an example of how the resolution indicates the quality of the structure (linked from original source):
In your case, the structure of the Spike glycoprotein (PDB code: 6VXX) has resolution of $2.80\,\overset{\circ}{\mathrm{A}}$ and the membrane protein (PDB code: 3I6G) has $2.20\,\overset{\circ}{\mathrm{A}}$. So, both structures are at the quality limit (a desired resolution for docking studies1 is resolution below $2.00\,\overset{\circ}{\mathrm{A}}$.
Another properties you have to worry about are the atomic charges, the protonation state, how to treat the flexibility (what residues will be considered flexible during the docking)2, and the presence of co-factors and ligands/substrates.
As the docking software will give you a still-image (a snap-shot conformation), it is recommended to run a Molecular Dynamics simulation using the pose obtained from the docking as input file.
The web server HADDOCK is specialized in protein-protein docking, and will take care of must of the properties mentioned above (except the resolution).
- Torsten Schwede & Manuel C. Peitsch. Computational Structural Biology: Methods and Applications. World Scientific Publishing Company. 2012. ISBN 9789812778772.
- Ideally, all the residues should be considered flexible, but this will increase the computational time.
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Another factor to consider might be blind docking or targeted. In this latter, only a region indicated on protein is targeted. In blind docking, the ligand will bind wherever suited on the protein while in targeted only the region indicated will be accessible to the ligand. Blind docking is closer to the real biological setting but computationally expensive. You might want to have a look here for blind docking.
