Might depend on what your measure of 'novelty' is in protein structure. A single residue change (for example) would not normally be considered a novel structure

Might depend on what your measure of 'novelty' is in protein structure. A single residue change (for example) would not normally be considered a novel structure - it's just a mutation. However, a new fold - that is, the shape that the backbone folds into - would be novel. Potentially also novel would be 'chimeric' structures with parts from other structures, as with chimeric domain swaps. There was a structure designed by the Baker lab called 'Top7 - https://pubmed.ncbi.nlm.nih.gov/14631033/ https://pubmed.ncbi.nlm.nih.gov/14631033/ that I remember as ground breaking at the time :) (in the ancient days of 2003 it seems ...)