Modelling the Fv/Constant Regions

A carefully built model of the Fv regions of the source antibody and in some cases the humanised antibody is a common denominator in many of the successful humanisation experiments. Nowadays, it is possible to build a model completely automatically using commercial packages or academic servers such as Swiss-Model. However, the danger of allowing a computer to make all the decisions is highlighted in the humanisation of antibody AT13/5 where the interaction between residues at positions 29 and 78 (Kabat numbering) in the heavy chain was not modelled correctly. The experience of an expert in protein structure modelling is always welcomed. Additionally, in the author's own humanisation experience, it is better to also model the constant regions of the antibody, since interactions at the variable/constant domain interface are likely to affect the avidity of the molecule.



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