Nanobodies are proteins derived from heavy chain-only antibodies and as a result, have unique properties. To study how a nanobody binds to the appropriate antigen, we can analyse the places in the structure where energy interactions are the strongest, called hot spots. To find such interactions in silico, the FoldX program can be used to perform an alanine scanning method, because of which we can evaluate how free energy changes in the nanobody-antigen complex. With that method, we found 652 hot spots in a dataset of 123 nanobody-antigen complexes. We found that the amino acid most represented in hot spots is tyrosine and that the majority can be found in the CDR3 region of the nanobody. Furthermore, there appears to be no correlation between the number of hot spots and contacts in each nanobody. The results could be one of the steps on the way to designing nanobodies for medical use.
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