Fast and flexible design of novel proteins using graph neural networks

Abstract

Protein structure and function is determined by the arrangement of the linear sequence of amino acids in 3D space. Despite substantial advances, precisely designing sequences that fold into a predetermined shape (the "protein design" problem) remains difficult. We show that a deep graph neural network, ProteinSolver, can solve protein design by phrasing it as a constraint satisfaction problem (CSP). To sidestep the considerable issue of optimizing the network architecture, we first develop a network that is accurately able to solve the related and straightforward problem of Sudoku puzzles. Recognizing that each protein design CSP has many solutions, we train this network on millions of real protein sequences corresponding to thousands of protein structures. We show that our method rapidly designs novel protein sequences and perform a variety of in silico and in vitro validations suggesting that our designed proteins adopt the predetermined structures. One Sentence SummaryA neural network optimized using Sudoku puzzles designs protein sequences that adopt predetermined structures.