Protein Sequence Design in a Latent Space via Model-based Reinforcement LearningDownload PDF

Published: 01 Feb 2023, Last Modified: 13 Feb 2023Submitted to ICLR 2023Readers: Everyone
Keywords: Biological sequence design, Model-based reinforcement learning, Protein design, Representation learning
TL;DR: This study investigates why many model-based biological sequence design methods produce results that empirically fail and proposes a novel optimization process that can efficiently traverse a latent representation space instead of the sequence space.
Abstract: Proteins are complex molecules responsible for different functions in the human body. Enhancing the functionality of a protein and/or cellular fitness can significantly impact various industries. However, their optimization remains challenging, and sequences generated by data-driven methods often fail in wet lab experiments. This study investigates the limitations of existing model-based sequence design methods and presents a novel optimization framework that can efficiently traverse the latent representation space instead of the protein sequence space. Our framework generates proteins with higher functionality and cellular fitness by modeling the sequence design task as a Markov decision process and applying model-based reinforcement learning. We discuss the results in a comprehensive evaluation of two distinct proteins, GPF and His3, along with the predicted structure of optimized sequences using deep learning-based structure prediction.
Anonymous Url: I certify that there is no URL (e.g., github page) that could be used to find authors’ identity.
No Acknowledgement Section: I certify that there is no acknowledgement section in this submission for double blind review.
Code Of Ethics: I acknowledge that I and all co-authors of this work have read and commit to adhering to the ICLR Code of Ethics
Submission Guidelines: Yes
Please Choose The Closest Area That Your Submission Falls Into: Machine Learning for Sciences (eg biology, physics, health sciences, social sciences, climate/sustainability )
Supplementary Material: zip
26 Replies