Design of overlapping genes using deep generative models of protein sequences.

ABSTRACT: In nature, viruses frequently evolve overlapping genes (OLG) in alternate reading frames of the same nucleotide sequence despite the drastically reduced protein sequence space resulting from the sharing of codon nucleotides. Their existence leads one to wonder whether amino acid sequences are sufficiently degenerate with respect to protein folding to broadly allow arbitrary pairs of functional proteins to be overlapped. Here, we investigate this question by engineering synthetic OLGs using state-of-the-art generative models. To evaluate the approach, we first design overlapped sequences targeting two different protein families. We then encode distinct highly ordered de novo protein structures and observe surprisingly high in silico and experimental success rates. This demonstrates that the

SUBMITTER: Byeon GW 

PROVIDER: S-EPMC12248029 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature