Ig-VAE: Generative modeling of protein structure by direct 3D coordinate generation

PLoS Comput Biol. 2022 Jun 27;18(6):e1010271. doi: 10.1371/journal.pcbi.1010271. eCollection 2022 Jun.

Abstract

While deep learning models have seen increasing applications in protein science, few have been implemented for protein backbone generation-an important task in structure-based problems such as active site and interface design. We present a new approach to building class-specific backbones, using a variational auto-encoder to directly generate the 3D coordinates of immunoglobulins. Our model is torsion- and distance-aware, learns a high-resolution embedding of the dataset, and generates novel, high-quality structures compatible with existing design tools. We show that the Ig-VAE can be used with Rosetta to create a computational model of a SARS-CoV2-RBD binder via latent space sampling. We further demonstrate that the model's generative prior is a powerful tool for guiding computational protein design, motivating a new paradigm under which backbone design is solved as constrained optimization problem in the latent space of a generative model.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19*
  • Humans
  • Immunoglobulins
  • Proteins / chemistry
  • RNA, Viral*
  • SARS-CoV-2

Substances

  • Immunoglobulins
  • Proteins
  • RNA, Viral