Inverse folding of CDRs benefits from span masking during training

Summary

Inverse folding of CDRs benefits from masking contiguous stretches of residues during training (1). This is in contrast to inverse folding of framework residues, which like generic proteins benefit from random masking (AKA “shotgun masking”; (2)).

Figures

Exp/Pred	Layer Decay	OAS Gaussian Noise	Test Masking	FR Avg.	CDR1H	CDR2H	CDR3H	CDR1L	CDR2L	CDR3L
Exp	-	-	None	0.898	0.731	0.712	0.569	0.723	0.736	0.718
Exp	-	✓	None	0.898	0.735	0.698	0.566	0.716	0.702	0.713
Exp	✓	-	None	0.895	0.741	0.700	0.584	0.716	0.741	0.725
Exp	✓	✓	None	0.894	0.727	0.702	0.573	0.720	0.728	0.727
Exp	-	-	CDRs	0.894	0.680	0.637	0.432	0.677	0.689	0.661
Exp	-	✓	CDRs	0.894	0.696	0.651	0.434	0.692	0.680	0.659
Exp	✓	-	CDRs	0.890	0.675	0.657	0.431	0.666	0.689	0.658
Exp	✓	✓	CDRs	0.891	0.681	0.653	0.430	0.666	0.698	0.655
Pred	-	-	None	0.909	0.753	0.716	0.561	0.738	0.731	0.722
Pred	-	✓	None	0.905	0.749	0.704	0.558	0.729	0.725	0.722
Pred	✓	-	None	0.907	0.750	0.730	0.572	0.746	0.737	0.730
Pred	✓	✓	None	0.903	0.744	0.713	0.554	0.744	0.733	0.718
Pred	-	-	CDRs	0.904	0.706	0.650	0.445	0.691	0.687	0.665
Pred	-	✓	CDRs	0.901	0.709	0.657	0.435	0.701	0.690	0.658
Pred	✓	-	CDRs	0.903	0.695	0.654	0.435	0.675	0.675	0.654
Pred	✓	✓	CDRs	0.898	0.699	0.647	0.433	0.682	0.682	0.658
Table from (1)

1.

Hoie M, Hummer A, Olsen T, Nielsen M, Deane C. AntiFold: Improved antibody structure design using inverse folding. In: GenBio@NeurIPS2023. 2023. Available from: https://openreview.net/forum?id=bxZMKHtlL6

2.

Hsu C, Verkuil R, Liu J, Lin Z, Hie B, Sercu T, et al. Learning inverse folding from millions of predicted structures. openRxiv; 2022. Available from: https://doi.org/10.1101/2022.04.10.487779