Multi-Chain Hamiltonian Replica Exchange Framework for Probing Transient Helices and Order-Disorder Transitions in Proteins
- 1Max Planck Institute for Polymer Research
Abstract
Simulations have emerged as a pillar in biophysics to understand behavior at the molecular scale, in particular for proteins such as intrinsically disordered proteins. These often show transient folding with long-lived states that are challenging to efficiently sample using conventional simulations. Here, we show that Hamiltonian replica-exchange at the level of hydrogen bonds can be used to systematically explore the conformational landscape of proteins. Investigating the IM30 protein, a partially alpha helical protein, under the PLUM coarse-grain force-field, we show that this approach straightforwardly allows characterization of local helix stability, which would be otherwise hard to obtain. For instance, we show that some regions of the conserved coiled-coil structure are less stable than others. By combining the different replicas with principal component analysis, we are able to dissect the conformational landscape of the IM30 protein. Taken together, this indicates that enhanced sampling remains an important part of simulations, allowing insights that cannot be easily obtained in traditional simulations.
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BibTeX
@misc{bhandari2026multichain,
title = {{Multi-Chain Hamiltonian Replica Exchange Framework for Probing Transient Helices and Order-Disorder Transitions in Proteins}},
author = {T. R. Bhandari and K. Kremer and M. Girard},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.755728},
url = {https://www.biorxiv.org/content/10.64898/2026.10.01.755728v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Multi-Chain Hamiltonian Replica Exchange Framework for Probing Transient Helices and Order-Disorder Transitions in Proteins
AU - T. R. Bhandari
AU - K. Kremer
AU - M. Girard
PY - 2026
DA - 2026/10/01
PB - bioRxiv
DO - 10.64898/2026.10.01.755728
UR - https://www.biorxiv.org/content/10.64898/2026.10.01.755728v1
AB - Simulations have emerged as a pillar in biophysics to understand behavior at the molecular scale, in particular for proteins such as intrinsically disordered proteins. These often show transient folding with long-lived states that are challenging to efficiently sample using conventional simulations. Here, we show that Hamiltonian replica-exchange at the level of hydrogen bonds can be used to systematically explore the conformational landscape of proteins. Investigating the IM30 protein, a partially alpha helical protein, under the PLUM coarse-grain force-field, we show that this approach straightforwardly allows characterization of local helix stability, which would be otherwise hard to obtain. For instance, we show that some regions of the conserved coiled-coil structure are less stable than others. By combining the different replicas with principal component analysis, we are able to dissect the conformational landscape of the IM30 protein. Taken together, this indicates that enhanced sampling remains an important part of simulations, allowing insights that cannot be easily obtained in traditional simulations.
ER -