Comparative Computational Approach to Study Enzyme Reactions Using QM and QM-MM Methods

Ibrahim Yildiz, Banu Sizirici Yildiz, Serdal Kirmizialtin

Research output: Contribution to journalArticle

Abstract

Choline oxidase catalyzes oxidation of choline into glycine betaine through a two-step reaction pathway employing flavin as the cofactor. On the light of kinetic studies, it is proposed that a hydride ion is transferred from α-carbon of choline/hydrated-betaine aldehyde to the N5 position of flavin in the rate-determining step, which is preceded by deprotonation of hydroxyl group of choline/hydrated-betaine aldehyde to one of the possible basic side chains. Using the crystal structure of glycine betaine-choline oxidase complex, we formulated two computational systems to study the hydride-transfer mechanism including main active-site amino acid side chains, flavin cofactor, and choline as a model system. The first system used pure density functional theory calculations, whereas the second approach used a hybrid ONIOM approach consisting of density functional and molecular mechanics calculations. We were able to formulate in silico model active sites to study the hydride-transfer steps by utilizing noncovalent chemical interactions between choline/betaine aldehyde and active-site amino acid chains using an atomistic approach. We evaluated and compared the geometries and energetics of hydride-transfer process using two different systems. We highlighted chemical interactions and studied the effect of protonation state of an active-site histidine base on the energetics of transfer. Furthermore, we evaluated energetics of the second hydride-transfer process as well as hydration of betaine aldehyde.

Original languageEnglish (US)
Pages (from-to)14689-14703
Number of pages15
JournalACS Omega
Volume3
Issue number11
DOIs
StatePublished - Nov 2 2018

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Betaines
Choline
Hydrides
choline oxidase
Enzymes
Aldehydes
Betaine
Amino acids
Amino Acids
Deprotonation
Molecular mechanics
Protonation
Histidine
Hydration
Hydroxyl Radical
Density functional theory
Carbon
Crystal structure
Ions
Oxidation

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Comparative Computational Approach to Study Enzyme Reactions Using QM and QM-MM Methods. / Yildiz, Ibrahim; Yildiz, Banu Sizirici; Kirmizialtin, Serdal.

In: ACS Omega, Vol. 3, No. 11, 02.11.2018, p. 14689-14703.

Research output: Contribution to journalArticle

Yildiz, Ibrahim ; Yildiz, Banu Sizirici ; Kirmizialtin, Serdal. / Comparative Computational Approach to Study Enzyme Reactions Using QM and QM-MM Methods. In: ACS Omega. 2018 ; Vol. 3, No. 11. pp. 14689-14703.
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