Polyformer: a generative framework for thermodynamic modeling of polymeric molecules

Fuente: arXiv
Saved in:
Bibliographic Details
Main Authors: Valentini, Alessio, Pekker, David, Liang, Chungwen, Martinez, Todd, Mukhopadhyay, Swagatam
Format: Preprint
Published: 2026
Subjects:
Online Access:
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1866915975327121408
author Valentini, Alessio
Pekker, David
Liang, Chungwen
Martinez, Todd
Mukhopadhyay, Swagatam
author_facet Valentini, Alessio
Pekker, David
Liang, Chungwen
Martinez, Todd
Mukhopadhyay, Swagatam
contents The classic paradigm of structural biology is that the sequence of a biomolecule (protein, nucleic acid, lipid, etc) determines its conformation (shape) which determines its biological function. Protein folding programs like AlphaFold address this paradigm by predicting the single best conformation given a sequence that defines the molecule. However, biomolecules are not static structures, and their conformational ensemble determines their function. We present the Polyformer -- a generative framework for thermodynamic modeling of polymeric molecules. Given the sequence and temperature (or another thermodynamic variable), the Polyformer generates conformations faithful to the molecule's thermodynamic conformational ensemble. It is the first generative model that solves three problems simultaneously: how does a molecule fold, what is its conformational ensemble, and how does the conformational ensemble change as we change physical temperature. As a concrete test case, we apply Polyformer to protein domains with 50-111 residues and report good agreement of model predictions to Molecular Dynamics (MD) trajectories.
format Preprint
id arxiv_https___arxiv_org_abs_2604_14241
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Polyformer: a generative framework for thermodynamic modeling of polymeric molecules
Valentini, Alessio
Pekker, David
Liang, Chungwen
Martinez, Todd
Mukhopadhyay, Swagatam
Biomolecules
Statistical Mechanics
Machine Learning
Quantitative Methods
The classic paradigm of structural biology is that the sequence of a biomolecule (protein, nucleic acid, lipid, etc) determines its conformation (shape) which determines its biological function. Protein folding programs like AlphaFold address this paradigm by predicting the single best conformation given a sequence that defines the molecule. However, biomolecules are not static structures, and their conformational ensemble determines their function. We present the Polyformer -- a generative framework for thermodynamic modeling of polymeric molecules. Given the sequence and temperature (or another thermodynamic variable), the Polyformer generates conformations faithful to the molecule's thermodynamic conformational ensemble. It is the first generative model that solves three problems simultaneously: how does a molecule fold, what is its conformational ensemble, and how does the conformational ensemble change as we change physical temperature. As a concrete test case, we apply Polyformer to protein domains with 50-111 residues and report good agreement of model predictions to Molecular Dynamics (MD) trajectories.
title Polyformer: a generative framework for thermodynamic modeling of polymeric molecules
topic Biomolecules
Statistical Mechanics
Machine Learning
Quantitative Methods
url https://arxiv.org/abs/2604.14241