Saved in:
| Main Authors: | , |
|---|---|
| Format: | Preprint |
| Published: |
2026
|
| Subjects: | |
| Online Access: | https://arxiv.org/abs/2601.05388 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1866912981140373504 |
|---|---|
| author | Airas, Justin Zhang, Bin |
| author_facet | Airas, Justin Zhang, Bin |
| contents | Implicit solvent models (ISMs) promise to deliver the accuracy of explicit solvent simulations at a fraction of the computational cost. However, despite decades of development, their accuracy has remained insufficient for many critical applications, particularly for simulating protein folding and the behavior of intrinsically disordered proteins. Developing a transferable, data-driven ISM that overcomes the limitations of traditional analytical formulas remains a central challenge in computational chemistry. Here we address this challenge by introducing a novel strategy that distills the evolutionary information learned by a protein language model, ESM3, into a computationally efficient graph neural network (GNN). We show that this GNN potential, trained on effective energies from ESM3, is robust enough to drive stable, long-timescale molecular dynamics simulations. When combined with a standard electrostatics term, our hybrid model accurately reproduces protein folding free-energy landscapes and predicts the structural ensembles of intrinsically disordered proteins. This approach yields a single, unified model that is transferable across both folded and disordered protein states, resolving a long-standing limitation of conventional ISMs. By successfully distilling evolutionary knowledge into a physical potential, our work delivers a foundational implicit solvent model poised to accelerate the development of predictive, large-scale simulation tools. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2601_05388 |
| institution | arXiv |
| publishDate | 2026 |
| record_format | arxiv |
| spellingShingle | Knowledge Distillation of a Protein Language Model Yields a Foundational Implicit Solvent Model Airas, Justin Zhang, Bin Biological Physics Chemical Physics Computational Physics Implicit solvent models (ISMs) promise to deliver the accuracy of explicit solvent simulations at a fraction of the computational cost. However, despite decades of development, their accuracy has remained insufficient for many critical applications, particularly for simulating protein folding and the behavior of intrinsically disordered proteins. Developing a transferable, data-driven ISM that overcomes the limitations of traditional analytical formulas remains a central challenge in computational chemistry. Here we address this challenge by introducing a novel strategy that distills the evolutionary information learned by a protein language model, ESM3, into a computationally efficient graph neural network (GNN). We show that this GNN potential, trained on effective energies from ESM3, is robust enough to drive stable, long-timescale molecular dynamics simulations. When combined with a standard electrostatics term, our hybrid model accurately reproduces protein folding free-energy landscapes and predicts the structural ensembles of intrinsically disordered proteins. This approach yields a single, unified model that is transferable across both folded and disordered protein states, resolving a long-standing limitation of conventional ISMs. By successfully distilling evolutionary knowledge into a physical potential, our work delivers a foundational implicit solvent model poised to accelerate the development of predictive, large-scale simulation tools. |
| title | Knowledge Distillation of a Protein Language Model Yields a Foundational Implicit Solvent Model |
| topic | Biological Physics Chemical Physics Computational Physics |
| url | https://arxiv.org/abs/2601.05388 |