Enzyme millisecond conformational dynamics do not catalyze the chemical step
Pisliakov, Andrei V ; Cao, Jie ; Kamerlin, Shina C L LU
and Warshel, Arieh
(2009)
In Proceedings of the National Academy of Sciences of the United States of America
106(41).
p.64-17359
- Abstract
The idea that enzymes catalyze reactions by dynamical coupling between the conformational motions and the chemical coordinates has recently attracted major experimental and theoretical interest. However, experimental studies have not directly established that the conformational motions transfer energy to the chemical coordinate, and simulating enzyme catalysis on the relevant timescales has been impractical. Here, we introduce a renormalization approach that transforms the energetics and dynamics of the enzyme to an equivalent low-dimensional system, and allows us to simulate the dynamical coupling on a ms timescale. The simulations establish, by means of several independent approaches, that the conformational dynamics is not remembered... (More)
The idea that enzymes catalyze reactions by dynamical coupling between the conformational motions and the chemical coordinates has recently attracted major experimental and theoretical interest. However, experimental studies have not directly established that the conformational motions transfer energy to the chemical coordinate, and simulating enzyme catalysis on the relevant timescales has been impractical. Here, we introduce a renormalization approach that transforms the energetics and dynamics of the enzyme to an equivalent low-dimensional system, and allows us to simulate the dynamical coupling on a ms timescale. The simulations establish, by means of several independent approaches, that the conformational dynamics is not remembered during the chemical step and does not contribute significantly to catalysis. Nevertheless, the precise nature of this coupling is a question of great importance.
(Less)
- author
- Pisliakov, Andrei V
; Cao, Jie
; Kamerlin, Shina C L
LU
and Warshel, Arieh
- publishing date
- 2009-10-13
- type
- Contribution to journal
- publication status
- published
- keywords
- Adenosine Monophosphate/metabolism, Adenosine Triphosphate/metabolism, Adenylate Kinase/chemistry, Calorimetry, Catalysis, Computer Simulation, Energy Transfer, Enzymes/chemistry, Kinetics, Ligands, Protein Binding, Protein Conformation, Thermodynamics
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 106
- issue
- 41
- pages
- 6 pages
- publisher
- National Academy of Sciences
- external identifiers
-
- scopus:70350453758
- pmid:19805169
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.0909150106
- language
- English
- LU publication?
- no
- id
- 9f54aefe-aa2f-483d-9151-946715c8d9c2
- date added to LUP
- 2025-01-11 22:15:49
- date last changed
- 2025-06-30 05:50:06
@article{9f54aefe-aa2f-483d-9151-946715c8d9c2,
abstract = {{<p>The idea that enzymes catalyze reactions by dynamical coupling between the conformational motions and the chemical coordinates has recently attracted major experimental and theoretical interest. However, experimental studies have not directly established that the conformational motions transfer energy to the chemical coordinate, and simulating enzyme catalysis on the relevant timescales has been impractical. Here, we introduce a renormalization approach that transforms the energetics and dynamics of the enzyme to an equivalent low-dimensional system, and allows us to simulate the dynamical coupling on a ms timescale. The simulations establish, by means of several independent approaches, that the conformational dynamics is not remembered during the chemical step and does not contribute significantly to catalysis. Nevertheless, the precise nature of this coupling is a question of great importance.</p>}},
author = {{Pisliakov, Andrei V and Cao, Jie and Kamerlin, Shina C L and Warshel, Arieh}},
issn = {{1091-6490}},
keywords = {{Adenosine Monophosphate/metabolism; Adenosine Triphosphate/metabolism; Adenylate Kinase/chemistry; Calorimetry; Catalysis; Computer Simulation; Energy Transfer; Enzymes/chemistry; Kinetics; Ligands; Protein Binding; Protein Conformation; Thermodynamics}},
language = {{eng}},
month = {{10}},
number = {{41}},
pages = {{64--17359}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences of the United States of America}},
title = {{Enzyme millisecond conformational dynamics do not catalyze the chemical step}},
url = {{http://dx.doi.org/10.1073/pnas.0909150106}},
doi = {{10.1073/pnas.0909150106}},
volume = {{106}},
year = {{2009}},
}