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

RR Eguchi, CA Choe, PS Huang - PLoS computational biology, 2022 - journals.plos.org
PLoS computational biology, 2022journals.plos.org
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 …
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.
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