Predicting protein stability changes under multiple amino acid substitutions using equivariant graph neural networks

The accurate prediction of changes in protein stability under multiple amino acid substitutions is essential for realising true in-silico protein re-design. To this purpose, we propose improvements to state-of-the-art Deep learning (DL) protein stability prediction models, enabling first of a kind predictions for variable numbers of amino acid substitutions. By decoupling the atomic and residue scales of protein representations, using E(3)-equivariant graph neural networks (EGNN) for both Atomic Environment (AE) embedding and residue level scoring tasks. OurAE embedder was used to featurise a residue level graph, then trained to score mutant stability (∆∆G). To achieve effective training of this predictive EGNN we have leveraged the unprecedented scale of a new high-throughput protein stability experimental data-set, Mega-scale. Finally, we demonstrate the immeadiately promising results of this procedure, discuss the current shortcomings, and highlight potential future strategies