Search arXiv⌕ Search
Home/Archive/arXiv

arXiv · 2508.00578

Learning Potential Energy Surfaces of Hydrogen Atom Transfer Reactions in Peptides

Marlen Neubert·Patrick Reiser·Frauke Gräter·Pascal Friederich
View original source ↗Read source document ↗Export metadata ↓

Abstract

Hydrogen atom transfer (HAT) reactions are essential in many biological processes, such as radical migration in damaged proteins, but their mechanistic pathways remain incompletely understood. Simulating HAT is challenging due to the need for quantum chemical accuracy at biologically relevant scales; thus, neither classical force fields nor DFT-based molecular dynamics are applicable. Machine-learned potentials offer an alternative, able to learn potential energy surfaces (PESs) with near-quantum accuracy. However, training these models to generalize across diverse HAT configurations, especially at radical positions in proteins, requires tailored data generation and careful model selection. Here, we systematically generate HAT configurations in peptides to build large datasets using semiempirical methods and DFT. We benchmark three graph neural network architectures (SchNet, Allegro, and MACE) on their ability to learn HAT PESs and indirectly predict reaction barriers from energy predictions. MACE consistently outperforms the others in energy, force, and barrier prediction, achieving a mean absolute error of 1.13 kcal/mol on out-of-distribution DFT barrier predictions. Using molecular dynamics, we show our MACE potential is stable, reactive, and generalizes beyond training data to model HAT barriers in collagen I. This accuracy enables integration of ML potentials into large-scale collagen simulations to compute reaction rates from predicted barriers, advancing mechanistic understanding of HAT and radical migration in peptides. We analyze scaling laws, model transferability, and cost-performance trade-offs, and outline strategies for improvement by combining ML potentials with transition state search algorithms and active learning. Our approach is generalizable to other biomolecular systems, enabling quantum-accurate simulations of chemical reactivity in complex environments.

Explore related subjects

cs.LGcond-mat.mtrl-sciphysics.chem-phphysics.comp-phq-bio.BM

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Marlen Neubert, Patrick Reiser, Frauke Gräter, Pascal Friederich. 2025-11-24. Learning Potential Energy Surfaces of Hydrogen Atom Transfer Reactions in Peptides. https://arxiv.org/abs/2508.00578

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Random Polytope Descriptors

We introduce a class of random polytopes which simultaneously generalizes several known constructions. While being fairly general, these polytopes are also computationally exceptionally benign. We indicate how these properties can be exploited for classification and clustering tasks in data analysis. Crucially, our construction lets users smoothly trade off between a tighter description of the data and faster computation.

cs.LG↗
arXiv2026

CurvFed: Curvature-Aligned Federated Learning for Fairness without Demographics

Modern human sensing applications often rely on data distributed across users and devices, where privacy concerns prevent centralized training. Federated Learning (FL) addresses this challenge by enabling collaborative model training without exposing raw data or attributes. However, achieving fairness in such settings remains difficult, as most human sensing datasets lack demographic labels, and FL's privacy guarantees limit the use of sensitive attributes. This paper introduces CurvFed: Curvature Aligned Federated Learning for Fairness without Demographics, a theoretically grounded framework that promotes fairness in FL without requiring any demographic or sensitive attribute information, a concept termed Fairness without Demographics (FWD), by optimizing the underlying loss landscape curvature. Building on the theory that equivalent loss landscape curvature corresponds to consistent model efficacy across sensitive attribute groups, CurvFed regularizes the top eigenvalue of the Fisher Information Matrix (FIM) as an efficient proxy for loss landscape curvature, both within and across clients. This alignment promotes uniform model behavior across diverse bias inducing factors, offering an attribute agnostic route to algorithmic fairness. CurvFed is especially suitable for real world human sensing FL scenarios involving single or multi user edge devices with unknown or multiple bias factors. We validated CurvFed through theoretical and empirical justifications, as well as comprehensive evaluations using three real world datasets and a deployment on a heterogeneous testbed of resource constrained devices. Additionally, we conduct sensitivity analyses on local training data volume, client sampling, communication overhead, resource costs, and runtime performance to demonstrate its feasibility for practical FL edge device deployment.

cs.LG↗
arXiv2026

Path Regularization: A Near-Complete and Optimal Nonasymptotic Generalization Theory for Multilayer Neural Networks and Double Descent Phenomenon

Path regularization has shown to be a very effective regularization to train neural networks, leading to a better generalization property than common regularizations i.e. weight decay, etc. We propose a first near-complete (as will be made explicit in the main text) nonasymptotic generalization theory for multilayer neural networks with path regularizations for general learning problems. In particular, it does not require the boundedness of the loss function, as is commonly assumed in the literature. Our theory goes beyond the bias-variance tradeoff and aligns with phenomena typically encountered in deep learning. It is therefore sharply different from other existing nonasymptotic generalization error bounds. More explicitly, we propose an explicit generalization error upper bound for multilayer neural networks with $σ(0)=0$ and sufficiently broad Lipschitz loss functions, without requiring the width, depth, or other hyperparameters of the neural network to approach infinity, a specific neural network architecture (e.g., sparsity), or boundedness of the loss function, while also taking approximation error into consideration. In particular, we solve an open problem proposed by Weinan E et. al. in 2020 regarding the approximation rates in generalized Barron spaces. Furthermore, we show the near-minimax optimality of our theory for regression problems with ReLU activations. Notably, our upper bound exhibits the famous double descent phenomenon for such networks, which is the most distinguished characteristic compared with other existing results. Our subsequent work will prove the matching lower bounds in the minimax sense, meaning that it is highly possible that our theory reveals the true underlying mechanism of the double descent phenomenon. We can also explain scaling law from this theory.

cs.LG↗