TY  - JOUR
A1  - Martini, Linda
A1  - Kells, Adam
A1  - Covino, Roberto
A1  - Hummer, Gerhard
A1  - Buchete, Nicolae-Viorel
A1  - Rosta, Edina
T1  - Variational identification of Markovian transition states
T2  - Physical review. X, Expanding access
N2  - 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.
KW  - Chemical Physics
KW  - Computational Physics
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44547
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-445471
SN  - 2160-3308
N1  - 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.
VL  - 7
IS  - 3, Art. 031060
SP  - 031060-1
EP  - 031060-14
PB  - The American Physical Society
CY  - College Park, Md.
ER  -