Barrier crossing in dihydrofolate reductase does not involve a rate-promoting vibration

Mariangela Dametto, Dimitri Antoniou, Steven D Schwartz

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

We have studied atomic motions during the chemical reaction catalysed by the enzyme dihydrofolate reductase of Escherichia coli (EcDHFR), an important enzyme for nucleic acid synthesis. In our earlier work on the enzymes human lactate dehydrogenase and purine nucleoside phosphorylase, we had identified fast sub-ps motions that are part of the reaction coordinate. We employed Transition Path Sampling (TPS) and our recently developed reaction coordinate identification methodology to investigate if such fast motions couple to the reaction in DHFR on the barrier-crossing timescale. While we identified some protein motions near the barrier crossing event, these motions do not constitute a compressive promoting vibration, and do not appear as a clearly identifiable protein component in reaction.

Original languageEnglish (US)
Pages (from-to)531-536
Number of pages6
JournalMolecular Physics
Volume110
Issue number9-10
DOIs
StatePublished - May 10 2012

Fingerprint

Tetrahydrofolate Dehydrogenase
Vibration
vibration
Enzymes
enzymes
Purine-Nucleoside Phosphorylase
L-Lactate Dehydrogenase
Escherichia coli
Nucleic Acids
Chemical reactions
Proteins
proteins
lactates
purines
nucleosides
dehydrogenases
Sampling
nucleic acids
Escherichia
chemical reactions

Keywords

  • enzymatic catalysis
  • kernel PCA
  • protein dynamics
  • reaction coordinate
  • TPS

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Condensed Matter Physics
  • Biophysics
  • Molecular Biology

Cite this

Barrier crossing in dihydrofolate reductase does not involve a rate-promoting vibration. / Dametto, Mariangela; Antoniou, Dimitri; Schwartz, Steven D.

In: Molecular Physics, Vol. 110, No. 9-10, 10.05.2012, p. 531-536.

Research output: Contribution to journalArticle

Dametto, Mariangela ; Antoniou, Dimitri ; Schwartz, Steven D. / Barrier crossing in dihydrofolate reductase does not involve a rate-promoting vibration. In: Molecular Physics. 2012 ; Vol. 110, No. 9-10. pp. 531-536.
@article{b049e9122d6a43558002a8ceb1d0a84a,
title = "Barrier crossing in dihydrofolate reductase does not involve a rate-promoting vibration",
abstract = "We have studied atomic motions during the chemical reaction catalysed by the enzyme dihydrofolate reductase of Escherichia coli (EcDHFR), an important enzyme for nucleic acid synthesis. In our earlier work on the enzymes human lactate dehydrogenase and purine nucleoside phosphorylase, we had identified fast sub-ps motions that are part of the reaction coordinate. We employed Transition Path Sampling (TPS) and our recently developed reaction coordinate identification methodology to investigate if such fast motions couple to the reaction in DHFR on the barrier-crossing timescale. While we identified some protein motions near the barrier crossing event, these motions do not constitute a compressive promoting vibration, and do not appear as a clearly identifiable protein component in reaction.",
keywords = "enzymatic catalysis, kernel PCA, protein dynamics, reaction coordinate, TPS",
author = "Mariangela Dametto and Dimitri Antoniou and Schwartz, {Steven D}",
year = "2012",
month = "5",
day = "10",
doi = "10.1080/00268976.2012.655337",
language = "English (US)",
volume = "110",
pages = "531--536",
journal = "Molecular Physics",
issn = "0026-8976",
publisher = "Taylor and Francis Ltd.",
number = "9-10",

}

TY - JOUR

T1 - Barrier crossing in dihydrofolate reductase does not involve a rate-promoting vibration

AU - Dametto, Mariangela

AU - Antoniou, Dimitri

AU - Schwartz, Steven D

PY - 2012/5/10

Y1 - 2012/5/10

N2 - We have studied atomic motions during the chemical reaction catalysed by the enzyme dihydrofolate reductase of Escherichia coli (EcDHFR), an important enzyme for nucleic acid synthesis. In our earlier work on the enzymes human lactate dehydrogenase and purine nucleoside phosphorylase, we had identified fast sub-ps motions that are part of the reaction coordinate. We employed Transition Path Sampling (TPS) and our recently developed reaction coordinate identification methodology to investigate if such fast motions couple to the reaction in DHFR on the barrier-crossing timescale. While we identified some protein motions near the barrier crossing event, these motions do not constitute a compressive promoting vibration, and do not appear as a clearly identifiable protein component in reaction.

AB - We have studied atomic motions during the chemical reaction catalysed by the enzyme dihydrofolate reductase of Escherichia coli (EcDHFR), an important enzyme for nucleic acid synthesis. In our earlier work on the enzymes human lactate dehydrogenase and purine nucleoside phosphorylase, we had identified fast sub-ps motions that are part of the reaction coordinate. We employed Transition Path Sampling (TPS) and our recently developed reaction coordinate identification methodology to investigate if such fast motions couple to the reaction in DHFR on the barrier-crossing timescale. While we identified some protein motions near the barrier crossing event, these motions do not constitute a compressive promoting vibration, and do not appear as a clearly identifiable protein component in reaction.

KW - enzymatic catalysis

KW - kernel PCA

KW - protein dynamics

KW - reaction coordinate

KW - TPS

UR - http://www.scopus.com/inward/record.url?scp=84861887134&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861887134&partnerID=8YFLogxK

U2 - 10.1080/00268976.2012.655337

DO - 10.1080/00268976.2012.655337

M3 - Article

VL - 110

SP - 531

EP - 536

JO - Molecular Physics

JF - Molecular Physics

SN - 0026-8976

IS - 9-10

ER -