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@ARTICLE{Voronin:888464,
author = {Voronin, Arthur and Weiel, Marie and Schug, Alexander},
title = {{I}ncluding residual contact information into
replica-exchange {MD} simulations significantly enriches
native-like conformations},
journal = {PLOS ONE},
volume = {15},
number = {11},
issn = {1932-6203},
address = {San Francisco, California, US},
publisher = {PLOS},
reportid = {FZJ-2020-04932},
pages = {e0242072 -},
year = {2020},
abstract = {Proteins are complex biomolecules which perform critical
tasks in living organisms. Knowledge of a protein’s
structure is essential for understanding its physiological
function in detail. Despite the incredible progress in
experimental techniques, protein structure determination is
still expensive, time-consuming, and arduous. That is why
computer simulations are often used to complement or
interpret experimental data. Here, we explore how in silico
protein structure determination based on replica-exchange
molecular dynamics (REMD) can benefit from including contact
information derived from theoretical and experimental
sources, such as direct coupling analysis or NMR
spectroscopy. To reflect the influence from erroneous and
noisy data we probe how false-positive contacts influence
the simulated ensemble. Specifically, we integrate varying
numbers of randomly selected native and non-native contacts
and explore how such a bias can guide simulations towards
the native state. We investigate the number of contacts
needed for a significant enrichment of native-like
conformations and show the capabilities and limitations of
this method. Adhering to a threshold of approximately $75\%$
true-positive contacts within a simulation, we obtain an
ensemble with native-like conformations of high quality. We
find that contact-guided REMD is capable of delivering
physically reasonable models of a protein’s structure.},
cin = {JSC},
ddc = {610},
cid = {I:(DE-Juel1)JSC-20090406},
pnm = {511 - Computational Science and Mathematical Methods
(POF3-511) / Forschergruppe Schug $(hkf6_20200501)$},
pid = {G:(DE-HGF)POF3-511 / $G:(DE-Juel1)hkf6_20200501$},
typ = {PUB:(DE-HGF)16},
pubmed = {33196676},
UT = {WOS:000595266800006},
doi = {10.1371/journal.pone.0242072},
url = {https://juser.fz-juelich.de/record/888464},
}