Inferring Dynamic Information from Protein Structures by Gaussian Integrals and Deep Learning.

Abstract

Protein dynamics are central to function, but experiments and molecular dynamics (MD) simulations remain costly, low-throughput, and difficult to compare across protocols. Scalable structure-based methods are needed to infer dynamics from static protein structures. We present a deep learning framework that predicts protein dynamics from 30-dimensional Gaussian integral (GI) descriptors of Cα backbone topology. Using 1,374 ATLAS protein chains with MD-derived RMSF, GI stratified proteins into fold-relevant clusters enriched for secondary structure, sequence homology, and ECOD families. An attention-based 1D-CNN classified flexible versus non-flexible proteins with test AUC = 0.772 and separated slow-mode- from fast-mode-dominated dynamics with AUC = 0.91. Regression models recovered mean RMSF (Pearson r = 0.72; R² = 0.46) and slow-mode RMSF more accurately (Pearson r = 0.83; R² = 0.62), supporting rapid inference of flexibility and collective-motion bias. Code and data are available on GitHub at: https://github.com/fvilicich/gaussian_integral/blob/main/gaussian_integral_classification.ipynb. Supplementary data are available at Bioinformatics online.