A tremendous thank you to Gabe and members of the Rocklin lab for their feedback! 8/8

And we explore how Ala and Gly insertions at the same position can have very different effects! 7/8

The Pin1 WW domain example illustrates how deletions can stabilize a domain by relieving backbone strain 6/8

Using the Rosetta energy function, we see that stabilizing deletions (but not insertions) are often found in regions of higher backbone strain 5/8

Additionally, we find that Rosetta’s energy function outperforms an ESM-IF based analysis in predicting mutational effects of stabilizing indels 4/8

Using ColabFold predicted structures of stabilized variants, we show that most indel mutations cause minimal structural perturbations 3/8

We analyzed 103 stabilizing amino acid indel mutants of 48 diverse natural and designed small protein domains 2/8