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Publication Abstract from PubMed

While deep learning has revolutionized protein structure prediction, almost all experimentally characterized de novo protein designs have been generated using physically based approaches such as Rosetta. Here we describe a deep learning-based protein sequence design method, ProteinMPNN, with outstanding performance in both in silico and experimental tests. On native protein backbones, ProteinMPNN has a sequence recovery of 52.4%, compared to 32.9% for Rosetta. The amino acid sequence at different positions can be coupled between single or multiple chains, enabling application to a wide range of current protein design challenges. We demonstrate the broad utility and high accuracy of ProteinMPNN using X-ray crystallography, cryoEM and functional studies by rescuing previously failed designs, made using Rosetta or AlphaFold, of protein monomers, cyclic homo-oligomers, tetrahedral nanoparticles, and target binding proteins.

Robust deep learning-based protein sequence design using ProteinMPNN.,Dauparas J, Anishchenko I, Bennett N, Bai H, Ragotte RJ, Milles LF, Wicky BIM, Courbet A, de Haas RJ, Bethel N, Leung PJY, Huddy TF, Pellock S, Tischer D, Chan F, Koepnick B, Nguyen H, Kang A, Sankaran B, Bera AK, King NP, Baker D Science. 2022 Sep 15:eadd2187. doi: 10.1126/science.add2187. PMID:36108050^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.