Leveraging elastic networks in a coarse-grained brownian simulation framework for protein conformational dynamics
- 1Karolinska Institutet
Abstract
Protein dynamics is fundamental to understand mechanisms. Although atomistic Molecular Dynamics (MD) remains the gold standard for predicting protein motions, its computational cost limits applications at large scales. Here, we present a coarse-grained (CG) simulation framework that combines Elastic Network Models (ENMs) with implicit-solvent Brownian Dynamics (BD) to efficiently generate protein conformational ensembles from native states. Benchmarking the method on more than 8,500 proteins against large datasets of atomistic MD trajectories and multi-state ensembles from Nucleic Magnetic Resonance (NMR), we show that short ENM-BD simulations can reproduce the residue fluctuation profiles and the dominant protein motions with remarkable accuracy. Correlations of residue fluctuations often exceeded 80%, with many proteins showing agreements above 90%, while Principal Component Analysis (PCA) revealed strong correspondences between the essential motions in the ENM-BD simulations and those observed in MD and NMR ensembles. Following CG-to-all-atom reconstruction and short energy minimization, the ENM-BD conformers also achieve high stereochemical quality, which enables their usage in downstream atomistic applications. Finally, we show that the stochastic dynamics emerging from BD trajectories closely aligns with the normal modes encoded in the underlying elastic network, highlighting that most of the intrinsic dynamics of proteins is already embedded in their native 3D topology.
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BibTeX
@misc{scaramozzino2026leveraging,
title = {{Leveraging elastic networks in a coarse-grained brownian simulation framework for protein conformational dynamics}},
author = {D. Scaramozzino and E. Ruggeri and M. Feshyna and B. H. Lee and L. Orellana},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.22.753665},
url = {https://www.biorxiv.org/content/10.64898/2026.09.22.753665v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Leveraging elastic networks in a coarse-grained brownian simulation framework for protein conformational dynamics
AU - D. Scaramozzino
AU - E. Ruggeri
AU - M. Feshyna
AU - B. H. Lee
AU - L. Orellana
PY - 2026
DA - 2026/09/22
PB - bioRxiv
DO - 10.64898/2026.09.22.753665
UR - https://www.biorxiv.org/content/10.64898/2026.09.22.753665v1
AB - Protein dynamics is fundamental to understand mechanisms. Although atomistic Molecular Dynamics (MD) remains the gold standard for predicting protein motions, its computational cost limits applications at large scales. Here, we present a coarse-grained (CG) simulation framework that combines Elastic Network Models (ENMs) with implicit-solvent Brownian Dynamics (BD) to efficiently generate protein conformational ensembles from native states. Benchmarking the method on more than 8,500 proteins against large datasets of atomistic MD trajectories and multi-state ensembles from Nucleic Magnetic Resonance (NMR), we show that short ENM-BD simulations can reproduce the residue fluctuation profiles and the dominant protein motions with remarkable accuracy. Correlations of residue fluctuations often exceeded 80%, with many proteins showing agreements above 90%, while Principal Component Analysis (PCA) revealed strong correspondences between the essential motions in the ENM-BD simulations and those observed in MD and NMR ensembles. Following CG-to-all-atom reconstruction and short energy minimization, the ENM-BD conformers also achieve high stereochemical quality, which enables their usage in downstream atomistic applications. Finally, we show that the stochastic dynamics emerging from BD trajectories closely aligns with the normal modes encoded in the underlying elastic network, highlighting that most of the intrinsic dynamics of proteins is already embedded in their native 3D topology.
ER -