Support field neural representation learner framework for learning stability landscapes in molecular geometry

Understanding the determinants of protein structural stability remains a central challenge in computational biology. While recent prediction models achieve high accuracy, they provide limited insight into why specific conformations persist or how topology and packing confer robustness. We introduce Support Field Neural Representation Learner (SF-NRL) framework, a framework that represents stability as a learnable scalar field shaped by persistent topological motifs and local density. Implemented as the SF-NRL framework, our approach integrates persistent homology, kernel density estimation, and equivariant geometric encoders to predict residue-level support values. These values correlate with biophysical markers such as RMSF and B-factors, capture fold-level motifs, and generalize across unseen structural classes. Unlike methods based on contact maps or empirical potentials, SF-NRL framework yields an interpretable energy-like landscape that reflects intrinsic stability. This work provides a theoretical and computational foundation for stability-aware modeling, linking topological insights with deep representation learning.

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Publication Details

Journal
npj Biomedical Innovations.
Published
2025-11-26
DOI
https://doi.org/10.1038/s44385-025-00045-7
Primary Topic
Topological and Geometric Data Analysis
Type
article
Field-Weighted Citation Impact
0.00

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article

Support field neural representation learner framework for learning stability landscapes in molecular geometry

Jianshi Wang
npj Biomedical Innovations.
Topological and Geometric Data Analysis
article

Support field neural representation learner framework for learning stability landscapes in molecular geometry

Jianshi Wang
article en

Abstract

Understanding the determinants of protein structural stability remains a central challenge in computational biology. While recent prediction models achieve high accuracy, they provide limited insight into why specific conformations persist or how topology and packing confer robustness. We introduce Support Field Neural Representation Learner (SF-NRL) framework, a framework that represents stability as a learnable scalar field shaped by persistent topological motifs and local density. Implemented as the SF-NRL framework, our approach integrates persistent homology, kernel density estimation, and equivariant geometric encoders to predict residue-level support values. These values correlate with biophysical markers such as RMSF and B-factors, capture fold-level motifs, and generalize across unseen structural classes. Unlike methods based on contact maps or empirical potentials, SF-NRL framework yields an interpretable energy-like landscape that reflects intrinsic stability. This work provides a theoretical and computational foundation for stability-aware modeling, linking topological insights with deep representation learning.

npj Biomedical Innovations.Vol. 2(1)
Osaka Shoin Women's University (JP), Protein Research Foundation (JP), The University of Tokyo (JP)
Japan Society for the Promotion of Science
Openalex Percentile: Top 63%
Topological and Geometric Data Analysis
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Support field neural representation learner framework for learning stability landscapes in molecular geometry — Jianshi Wang · npj Biomedical Innovations. (2025) | TGRS Research Map | TGRS