Conditional Generative Modeling for De Novo Hierarchical Multi-Label Functional Protein Design

Tim Kucera, Karsten Michael Borgwardt, Matteo Togninalli, Laetitia Papaxanthos

Keywords: protein design, conditional generative adversarial networks, gene ontology, hierarchical multi-label, GO, GAN

Abstract: The availability of vast protein sequence information and rich functional annotations thereof has a large potential for protein design applications in biomedicine and synthetic biology. To this date, there exists no method for the general-purpose design of proteins without any prior knowledge about the protein of interest, such as costly and rare structure information or seed sequence fragments. However, the Gene Ontology (GO) database provides information about the hierarchical organisation of protein functions, and thus could inform generative models about the underlying complex sequence-function relationships, replacing the need for structural data. We therefore propose to use conditional generative adversarial networks (cGANs) on the task of fast de novo hierarchical multi-label protein design. We generate protein sequences exhibiting properties of a large set of molecular functions extracted from the GO database, using a single model and without any prior information. We shed light on efficient conditioning mechanisms and adapted network architectures thanks to a thorough hyperparameter selection process and analysis. We further provide statistically- and biologically-driven evaluation measures for generative models in the context of protein design to assess the quality of the generated sequences and facilitate progress in the field. We show that our proposed model, ProteoGAN, outperforms several baselines when designing proteins given a functional label and generates well-formed sequences.

One-sentence Summary: We develop a conditional Generative Adversarial Network for sequence-based protein design with hierarchical multi-label gene ontology annotations.

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