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Including residual contact information into replica-exchange MD simulations significantly enriches native-like conformations

Voronin, Arthur 1,2; Weiel, Marie 1,2; Schug, Alexander
1 Fakultät für Physik (PHYSIK), Karlsruher Institut für Technologie (KIT)
2 Steinbuch Centre for Computing (SCC), Karlsruher Institut für Technologie (KIT)


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. ... mehr

Verlagsausgabe §
DOI: 10.5445/IR/1000126953
Veröffentlicht am 01.12.2020
DOI: 10.1371/journal.pone.0242072
Zitationen: 1
Zitationen: 2
Cover der Publikation
Zugehörige Institution(en) am KIT Steinbuch Centre for Computing (SCC)
Universität Karlsruhe (TH) – Zentrale Einrichtungen (Zentrale Einrichtungen)
Publikationstyp Zeitschriftenaufsatz
Publikationsdatum 16.11.2020
Sprache Englisch
Identifikator ISSN: 1932-6203
KITopen-ID: 1000126953
HGF-Programm 46.11.01 (POF III, LK 01) Computational Science and Mathematical Methods
Erschienen in PLOS ONE
Verlag Public Library of Science (PLoS)
Band 15
Heft 11
Seiten Art.-Nr.: e0242072
Nachgewiesen in Dimensions
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