Generative Models for Graph-Based Protein Design

John Ingraham, Vikas K. Garg, Regina Barzilay, Tommi Jaakkola

TL;DR: We learn to conditionally generate protein sequences given structures with a model that captures sparse, long-range dependencies.

Abstract: Engineered proteins offer the potential to solve many problems in biomedicine, energy, and materials science, but creating designs that succeed is difficult in practice. A significant aspect of this challenge is the complex coupling between protein sequence and 3D structure, and the task of finding a viable design is often referred to as the inverse protein folding problem. We develop generative models for protein sequences conditioned on a graph-structured specification of the design target. Our approach efficiently captures the complex dependencies in proteins by focusing on those that are long-range in sequence but local in 3D space. Our framework significantly improves upon prior parametric models of protein sequences given structure, and takes a step toward rapid and targeted biomolecular design with the aid of deep generative models.