Quantitative Biology > Biomolecules
arXiv:2206.04119 (q-bio)
[Submitted on 8 Jun 2022 (v1), last revised 20 Mar 2023 (this version, v2)]
Title:Diffusion probabilistic modeling of protein backbones in 3D for the motif-scaffolding problem
Authors:Brian L. Trippe,Jason Yim,Doug Tischer,David Baker,Tamara Broderick,Regina Barzilay,Tommi Jaakkola
View a PDF of the paper titled Diffusion probabilistic modeling of protein backbones in 3D for the motif-scaffolding problem, by Brian L. Trippe and 6 other authors
View PDFAbstract:Construction of a scaffold structure that supports a desired motif, conferring protein function, shows promise for the design of vaccines and enzymes. But a general solution to this motif-scaffolding problem remains open. Current machine-learning techniques for scaffold design are either limited to unrealistically small scaffolds (up to length 20) or struggle to produce multiple diverse scaffolds. We propose to learn a distribution over diverse and longer protein backbone structures via an E(3)-equivariant graph neural network. We develop SMCDiff to efficiently sample scaffolds from this distribution conditioned on a given motif; our algorithm is the first to theoretically guarantee conditional samples from a diffusion model in the large-compute limit. We evaluate our designed backbones by how well they align with AlphaFold2-predicted structures. We show that our method can (1) sample scaffolds up to 80 residues and (2) achieve structurally diverse scaffolds for a fixed motif.
| Comments: | Appearing in ICLR 2023. Code available:this http URL |
| Subjects: | Biomolecules (q-bio.BM); Machine Learning (cs.LG); Machine Learning (stat.ML) |
| Cite as: | arXiv:2206.04119 [q-bio.BM] |
| (orarXiv:2206.04119v2 [q-bio.BM] for this version) | |
| https://doi.org/10.48550/arXiv.2206.04119 arXiv-issued DOI via DataCite |
Submission history
From: Brian Trippe [view email][v1] Wed, 8 Jun 2022 18:35:08 UTC (20,407 KB)
[v2] Mon, 20 Mar 2023 00:22:03 UTC (11,087 KB)
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View a PDF of the paper titled Diffusion probabilistic modeling of protein backbones in 3D for the motif-scaffolding problem, by Brian L. Trippe and 6 other authors
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