Rotamer Density Estimator is an Unsupervised Learner of the Effect of Mutations on Protein-Protein InteractionDownload PDF

Published: 01 Feb 2023, Last Modified: 28 Feb 2023ICLR 2023 posterReaders: Everyone
Keywords: effect of mutations, protein-protein interaction, unsupervised learning
Abstract: Protein-protein interactions are crucial to many biological processes, and predicting the effect of amino acid mutations on binding is important for protein engineering. While data-driven approaches using deep learning have shown promise, the scarcity of annotated experimental data remains a major challenge. In this work, we propose a new approach that predicts mutational effects on binding using the change in conformational flexibility of the protein-protein interface. Our approach, named Rotamer Density Estimator (RDE), employs a flow-based generative model to estimate the probability distribution of protein side-chain conformations and uses entropy to measure flexibility. RDE is trained solely on protein structures and does not require the supervision of experimental values of changes in binding affinities. Furthermore, the unsupervised representations extracted by RDE can be used for downstream neural network predictions with even greater accuracy. Our method outperforms empirical energy functions and other machine learning-based approaches.
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 )
11 Replies