Preliminary results from Immunotherapy design puzzle (539)
Here are some preliminary results from the first Immunotherapy design puzzle (539). The results you generated were very interesting and we are still in the process of analyzing them. But to give you a glance at some useful structures we've posted a gallery puzzle where you can view them and play around.
In general 85% of the top-1000 scoring structures (as ranked by the Rosetta score) made use of the pronounced cavity between the two loops on the CTLA-4 protein. To give you some insight of the different binding modes a cool statistic to look at is the type of cavity residue. Looking at the type of cavity residues, there was a diversity between several hydrophobic residues as can be seen in this table:
Cavity residue Abundance
This diversity helps us to obtain useful hits, since the solutions were not directed towards one species inside the cavity. We do not only consider the Rosetta Score (which is your only guide), we also evaluate the binding energy between the 3 amino acids and the protein and we consider the resemblance of the two partners with regard to their shape. This gives us an indication how well your solutions will bind CTLA-4 when we actually produce them.
In the gallery we present three interesting solutions you came up with:
Foldit Player JackWeaver's solution: http://fold.it/portal/node/992496
Foldit Player Mark-'s solution: http://fold.it/portal/node/992497
Foldit Player Flagg65a's solution: http://fold.it/portal/node/992499
We have posted a new Immunotherapy design puzzle:
and will have a Scientist Chat to discuss it: