Scalable Normalizing Flows Enable Boltzmann Generators for Macromolecules
Primary Area: applications to physical sciences (physics, chemistry, biology, etc.)
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.
Keywords: normalizing flow, protein conformations, boltzmann generators, generative models
Submission Guidelines: I certify that this submission complies with the submission instructions as described on https://iclr.cc/Conferences/2024/AuthorGuide.
Abstract: The Boltzmann distribution of a protein provides a roadmap to all of its functional states. Normalizing flows are a promising tool for modeling this distribution, but current methods are intractable for typical pharmacological targets; they become computationally intractable due to the size of the system, heterogeneity of intra-molecular potential energy, and long-range interactions. To remedy these issues, we present a novel flow architecture that utilizes split channels and gated attention to efficiently learn the conformational distribution of proteins defined by internal coordinates. We show that by utilizing a 2-Wasserstein loss, one can smooth the transition from maximum likelihood training to energy-based training, enabling the training of Boltzmann Generators for macromolecules. We evaluate our model and training strategy on villin headpiece HP35(nle-nle), a 35-residue subdomain, and protein G, a 56-residue protein. We demonstrate that standard architectures and training strategies, such as maximum likelihood alone, fail while our novel architecture and multi-stage training strategy are able to model the conformational distributions of protein G and HP35.
Anonymous Url: I certify that there is no URL (e.g., github page) that could be used to find authors' identity.
Supplementary Material: pdf
No Acknowledgement Section: I certify that there is no acknowledgement section in this submission for double blind review.
Submission Number: 8285
Loading