Conformational Effects on the pro-S Hydrogen Abstraction Reaction in Cyclooxygenase-1: An Integrated QM/MM and MD Study

Christo Z. Christov; Alessio Lodola; Tatyana G. Karabencheva-Christova; Shunzhou Wan; Peter V. Coveney; Adrian J. Mulholland

doi:10.1016/j.bpj.2013.01.040

Conformational Effects on the pro-S Hydrogen Abstraction Reaction in Cyclooxygenase-1: An Integrated QM/MM and MD Study

Christo Z. Christov, Alessio Lodola, Tatyana G. Karabencheva-Christova, Shunzhou Wan, Peter V. Coveney, Adrian J. Mulholland^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

A key step in the cyclooxygenase reaction cycle of cyclooxygenase 1 (COX-1) is abstraction of the pro-S hydrogen atom of the arachidonic acid by a radical that is formed at the protein residue Tyr-385. Here we investigate this reaction step by a quantum-mechanics/molecular-mechanics approach in combination with molecular-dynamics simulations. The simulations identify the hydrogen abstraction angle as a crucial geometric determinant of the reaction, thus revealing the importance of the cyclooxygenase active site for calculating the potential energy surface of the reaction.

Original language	English
Pages (from-to)	L5-L7
Number of pages	3
Journal	Biophysical Journal
Volume	104
Issue number	5
DOIs	https://doi.org/10.1016/j.bpj.2013.01.040
Publication status	Published - 5 Mar 2013

Research Groups and Themes

Physical & Theoretical

Keywords

ACID AMIDE HYDROLASE
ENZYME CATALYSIS
DYNAMICS
SYNTHASE

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10.1016/j.bpj.2013.01.040

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CCP-BioSim: Biomolecular simulation at the life sciences interface
Mulholland, A. J. (Principal Investigator)
1/10/11 → 1/10/15
Project: Research
COMPUTATIONAL BIOCHEMISTRY: PREDICTIVE MODELLING FOR BIOLOGY AND MEDICINE
Mulholland, A. J. (Principal Investigator)
1/10/08 → 1/04/14
Project: Research

Cite this

@article{2bda5f381f4744678639ed722474b40e,

title = "Conformational Effects on the pro-S Hydrogen Abstraction Reaction in Cyclooxygenase-1: An Integrated QM/MM and MD Study",

abstract = "A key step in the cyclooxygenase reaction cycle of cyclooxygenase 1 (COX-1) is abstraction of the pro-S hydrogen atom of the arachidonic acid by a radical that is formed at the protein residue Tyr-385. Here we investigate this reaction step by a quantum-mechanics/molecular-mechanics approach in combination with molecular-dynamics simulations. The simulations identify the hydrogen abstraction angle as a crucial geometric determinant of the reaction, thus revealing the importance of the cyclooxygenase active site for calculating the potential energy surface of the reaction.",

keywords = "ACID AMIDE HYDROLASE, ENZYME CATALYSIS, DYNAMICS, SYNTHASE",

author = "Christov, \{Christo Z.\} and Alessio Lodola and Karabencheva-Christova, \{Tatyana G.\} and Shunzhou Wan and Coveney, \{Peter V.\} and Mulholland, \{Adrian J.\}",

year = "2013",

month = mar,

day = "5",

doi = "10.1016/j.bpj.2013.01.040",

language = "English",

volume = "104",

pages = "L5--L7",

journal = "Biophysical Journal",

issn = "0006-3495",

publisher = "Elsevier B.V.",

number = "5",

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TY - JOUR

T1 - Conformational Effects on the pro-S Hydrogen Abstraction Reaction in Cyclooxygenase-1: An Integrated QM/MM and MD Study

AU - Christov, Christo Z.

AU - Lodola, Alessio

AU - Karabencheva-Christova, Tatyana G.

AU - Wan, Shunzhou

AU - Coveney, Peter V.

AU - Mulholland, Adrian J.

PY - 2013/3/5

Y1 - 2013/3/5

N2 - A key step in the cyclooxygenase reaction cycle of cyclooxygenase 1 (COX-1) is abstraction of the pro-S hydrogen atom of the arachidonic acid by a radical that is formed at the protein residue Tyr-385. Here we investigate this reaction step by a quantum-mechanics/molecular-mechanics approach in combination with molecular-dynamics simulations. The simulations identify the hydrogen abstraction angle as a crucial geometric determinant of the reaction, thus revealing the importance of the cyclooxygenase active site for calculating the potential energy surface of the reaction.

AB - A key step in the cyclooxygenase reaction cycle of cyclooxygenase 1 (COX-1) is abstraction of the pro-S hydrogen atom of the arachidonic acid by a radical that is formed at the protein residue Tyr-385. Here we investigate this reaction step by a quantum-mechanics/molecular-mechanics approach in combination with molecular-dynamics simulations. The simulations identify the hydrogen abstraction angle as a crucial geometric determinant of the reaction, thus revealing the importance of the cyclooxygenase active site for calculating the potential energy surface of the reaction.

KW - ACID AMIDE HYDROLASE

KW - ENZYME CATALYSIS

KW - DYNAMICS

KW - SYNTHASE

U2 - 10.1016/j.bpj.2013.01.040

DO - 10.1016/j.bpj.2013.01.040

M3 - Article (Academic Journal)

C2 - 23473504

SN - 0006-3495

VL - 104

SP - L5-L7

JO - Biophysical Journal

JF - Biophysical Journal

IS - 5

ER -

Conformational Effects on the pro-S Hydrogen Abstraction Reaction in Cyclooxygenase-1: An Integrated QM/MM and MD Study

Abstract

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Projects

CCP-BioSim: Biomolecular simulation at the life sciences interface

COMPUTATIONAL BIOCHEMISTRY: PREDICTIVE MODELLING FOR BIOLOGY AND MEDICINE

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