Submission Details

Design Rationale:

The cleft near the binding site is visually similar to some of the collagen receptors I had worked with. Initially, I had docked a collagen triple helical backbone into the active site and then manually added the residues that could be accommodated. The rational for using a collagen triple helix was that is highly protease resistant, is easily absorbed in the gut and has low renal clearance. A major disadvantage is that it will probably not permeate the cell membrane as well as small molecules. In any case, I realised that all interactions were coming from a contiguous stretch of six amino acids GFRGFS on a single chain of the triple helix. Thus, I sopped working with then triple helix and instead docked the hexamer GFRGFS onto the domains harbouring the binding site in cluspro. Cluspro identified a single high energy cluster containing close to 1000 poses (uploaded). All the remaining 9 clusters also put the peptide within binding site albeit in slightly altered conformations. Variations on the sequence that give similar energies and cluster sizes in Cluspro are includes. Please note that we have converted this peptide into a peptidomimetic structure and are now working on docking it to the target. We will upload the results if the docking results look promising.

Inspired By:

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