Epitope scaffold search
How to search proteins having a given 3D secondary structure in the Protein Data Bank ?
Let's say that you have the structure of an antigen, it could be a few residues or as large as a protein-protein interaction surface. You will want to identify proteins than have the same 3D secondary structure on its surface. The search is based on finding a protein match between query and hit with similar positions of alpha carbon and orientation of the sidechains.
To focus on the most relevant results, compute and check if the proximate chains in the query (chains bound to the epitope) are likely to bind without too many bumps to the hit proteins.
So you will identify from the PDB, proteins likely to have similar interaction as the one in the query. Please note that the kind of sidechain is not checked in this tutorial, so you can identify hits with similar residues or not.
Ofek et al. searched the PDB for mimotopes of HIV1 gp41 epitope.They have reported 5 protein structures as parents of epitope scaffolds of the gp41 epitope. They designed epitope scaffolds from those parents, like ES2 from 1KU2 PDB file (Thermus aquaticus RNA Polymerase Sigma Subunit Fragment). They have shown the interest of searching mimotopes of GP41. In this tutorial, we show how MED-SuMo can retrieve the same computational results and also many others proteins from the PDB which are likely to be candidate for Protein Vaccine (with some protein engeneering on the sidechains.
The Query is built from 1TJI PDB file (released in 2004) and is the gp41 epitope (ELLELDKWASL) bound to the antibody 2F5. Then the whole PDB is mined for this epitope.
The files shown and the Graphical User Interface available for free trial in the download section of this website (please login using a valid email address).
The following video is describing the search of epitope scaffold and the analysis of the results:
More online videos are available in the learning center.
This work is based on the research work :
Ofek G, Guenaga FJ, Schief WR, Skinner J, Baker D, Wyatt R, Kwong PD. Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17880-7.