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Variational identification of Markovian transition states
- We present a method that enables the identification and analysis of conformational Markovian transition states from atomistic or coarse-grained molecular dynamics (MD) trajectories. Our algorithm is presented by using both analytical models and examples from MD simulations of the benchmark system helix-forming peptide Ala5, and of larger, biomedically important systems: the 15-lipoxygenase-2 enzyme (15-LOX-2), the epidermal growth factor receptor (EGFR) protein, and the Mga2 fungal transcription factor. The analysis of 15-LOX-2 uses data generated exclusively from biased umbrella sampling simulations carried out at the hybrid ab initio density functional theory (DFT) quantum mechanics/molecular mechanics (QM/MM) level of theory. In all cases, our method automatically identifies the corresponding transition states and metastable conformations in a variationally optimal way, with the input of a set of relevant coordinates, by accurately reproducing the intrinsic slowest relaxation rate of each system. Our approach offers a general yet easy-to-implement analysis method that provides unique insight into the molecular mechanism and the rare but crucial (i.e., rate-limiting) transition states occurring along conformational transition paths in complex dynamical systems such as molecular trajectories.
Verfasserangaben: | Linda Martini, Adam Kells, Roberto CovinoORCiD, Gerhard HummerORCiD, Nicolae-Viorel Buchete, Edina Rosta |
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URN: | urn:nbn:de:hebis:30:3-445471 |
DOI: | https://doi.org/10.1103/PhysRevX.7.031060 |
ISSN: | 2160-3308 |
Titel des übergeordneten Werkes (Englisch): | Physical review. X, Expanding access |
Verlag: | The American Physical Society |
Verlagsort: | College Park, Md. |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 07.11.2017 |
Datum der Erstveröffentlichung: | 28.09.2017 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 07.11.2017 |
Freies Schlagwort / Tag: | Chemical Physics; Computational Physics |
Jahrgang: | 7 |
Ausgabe / Heft: | 3, Art. 031060 |
Seitenzahl: | 14 |
Erste Seite: | 031060-1 |
Letzte Seite: | 031060-14 |
Bemerkung: | Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI. |
HeBIS-PPN: | 428738680 |
Institute: | Physik / Physik |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 53 Physik / 530 Physik |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | Creative Commons - Namensnennung 4.0 |