I have used ROSIE server to analyze protein-antibody interaction and predict peptide sequences of antibody that would interact with the protein.
The analysis revealed 3 hotspots of the antibody sequence as in the picture attached. It did make sense to me that the predicted linaer peptides from antibody sequence were chosen from 1st and 3rd hotspots from the figure with highest contact points with the protein.
However, in cyclic peptide predictions, the server did predict only one cyclic peptide based on the middle hotspot in this figure. I do not understand the rational for that. How can the hotspot with least contact points with the protein give the best predicition for interaction upon cyclization. And why no other cyclic peptides were predicted based on the other 2 main hotspots in the interaction.