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An enumerative algorithm for de novo design of proteins with diverse pocket structures

2020; National Academy of Sciences; Volume: 117; Issue: 36 Linguagem: Inglês

10.1073/pnas.2005412117

1091-6490

Benjamin Basanta, Matthew J. Bick, Asim K. Bera, Christoffer Norn, Cameron M. Chow, Lauren Carter, Inna Goreshnik, Frank DiMaio, David Baker,

Enzyme Structure and Function

Significance Reengineering naturally occurring proteins to have new functions has had considerable impact on industrial and biomedical applications, but is limited by the finite number of known proteins. A promise of de novo protein design is to generate a larger and more diverse set of protein structures than is currently available. This vision has not yet been realized for small-molecule binder or enzyme design due to the complexity of pocket-containing structures. Here we present an algorithm that systematically generates NTF2-like protein structures with diverse pocket geometries. The scaffold sets, the insights gained from detailed structural characterization, and the computational method for generating unlimited numbers of structures should contribute to a new generation of de novo small-molecule binding proteins and catalysts.