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A structure-based deep learning framework for protein engineering

Shroff, R.; Cole, A. W.; Morrow, B. R.; Diaz, D. J.; Donnell, I.; Gollihar, J.; Ellington, A. D.; Thyer, R.

2019-11-08 synthetic biology
10.1101/833905 bioRxiv
Show abstract

While deep learning methods exist to guide protein optimization, examples of novel proteins generated with these techniques require a priori mutational data. Here we report a 3D convolutional neural network that associates amino acids with neighboring chemical microenvironments at state-of-the-art accuracy. This algorithm enables identification of novel gain-of-function mutations, and subsequent experiments confirm substantive phenotypic improvements in stability-associated phenotypes in vivo across three diverse proteins.

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