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.
Author: | Linda Martini, Adam Kells, Roberto CovinoORCiD, Gerhard HummerORCiD, Nicolae-Viorel Buchete, Edina Rosta |
---|---|
URN: | urn:nbn:de:hebis:30:3-445471 |
DOI: | https://doi.org/10.1103/PhysRevX.7.031060 |
ISSN: | 2160-3308 |
Parent Title (English): | Physical review. X, Expanding access |
Publisher: | The American Physical Society |
Place of publication: | College Park, Md. |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2017/11/07 |
Date of first Publication: | 2017/09/28 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2017/11/07 |
Tag: | Chemical Physics; Computational Physics |
Volume: | 7 |
Issue: | 3, Art. 031060 |
Page Number: | 14 |
First Page: | 031060-1 |
Last Page: | 031060-14 |
Note: | 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 |
Institutes: | Physik / Physik |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 53 Physik / 530 Physik |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |