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@ARTICLE{Schffler:1047546,
author = {Schäffler, Moritz and Wales, David J. and Strodel, Birgit},
title = {{E}nergy {L}andscape and {K}inetic {A}nalysis of
{M}olecular {D}ynamics {S}imulations for {I}ntrinsically
{D}isordered {P}roteins},
journal = {The journal of physical chemistry / B},
volume = {129},
number = {44},
issn = {1520-6106},
address = {Washington, DC},
publisher = {Americal Chemical Society},
reportid = {FZJ-2025-04372},
pages = {11430-11440},
year = {2025},
abstract = {Understanding the conformational dynamics of biomolecules
requires methods that go beyond structural sampling and
provide a quantitative description of thermodynamics and
kinetics. For intrinsically disordered proteins (IDPs),
energy landscape characterization is particularly crucial to
unravel their complex conformational behavior. Here, we
present a comprehensive protocol for analyzing molecular
dynamics (MD) simulations in terms of energy landscapes,
metastable states, and transition pathways. Our approach is
based on the distribution of reciprocal interatomic
distances (DRID) for dimensionality reduction, followed by
clustering and kinetic modeling. Free energy surfaces and
transition state barriers are computed directly from the
simulation data and visualized using disconnectivity graphs.
The method integrates two Python packages, DRIDmetric and
freenet, with standard energy landscape tools based on
kinetic transition networks, including PATHSAMPLE and
disconnectionDPS. We demonstrate this workflow for
simulations of the intrinsically disordered,
aggregation-prone Alzheimer’s amyloid-β peptide in
physiologically relevant environments. This modular
framework offers a robust and interpretable way to extract
thermodynamic and kinetic insights from MD data and is
especially valuable for characterizing the diverse
conformational states of IDPs.},
cin = {IBI-7},
ddc = {530},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
doi = {10.1021/acs.jpcb.5c05390},
url = {https://juser.fz-juelich.de/record/1047546},
}