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Sampling of the conformational landscape of small proteins with Monte Carlo methods

Heilmann, Nana 1; Wolf, Moritz 1; Kozlowska, Mariana ORCID iD icon 1; Sedghamiz, Elaheh 1; Setzler, Julia 1; Brieg, Martin 1; Wenzel, Wolfgang 1
1 Institut für Nanotechnologie (INT), Karlsruher Institut für Technologie (KIT)


Computer simulation provides an increasingly realistic picture of large-scale conformational change of proteins, but investigations remain fundamentally constrained by the femtosecond timestep of molecular dynamics simulations. For this reason, many biologically interesting questions cannot be addressed using accessible state-of-the-art computational resources. Here, we report the development of an all-atom Monte Carlo approach that permits the modelling of the large-scale conformational change of proteins using standard off-the-shelf computational hardware and standard all-atom force fields. We demonstrate extensive thermodynamic characterization of the folding process of the α-helical Trp-cage, the Villin headpiece and the β-sheet WW-domain. We fully characterize the free energy landscape, transition states, energy barriers between different states, and the per-residue stability of individual amino acids over a wide temperature range. We demonstrate that a state-of-the-art intramolecular force field can be combined with an implicit solvent model to obtain a high quality of the folded structures and also discuss limitations that still remain.

Verlagsausgabe §
DOI: 10.5445/IR/1000126007
Veröffentlicht am 13.11.2020
DOI: 10.1038/s41598-020-75239-7
Zitationen: 20
Zitationen: 27
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Nanotechnologie (INT)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2020
Sprache Englisch
Identifikator ISSN: 2045-2322
KITopen-ID: 1000126007
HGF-Programm 43.21.04 (POF III, LK 01) Molecular Engineering
Erschienen in Scientific reports
Verlag Nature Research
Band 10
Seiten Art.-Nr.: 18211
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