Structural insights into human microsomal epoxide hydrolase by combined homology modeling, molecular dynamics simulations, and molecular docking calculations

• A new homology model of human microsomal epoxide hydrolase was derived based on multiple templates. The model obtained was fully evaluated, including MD simulations and ensemble-based docking, showing that the quality of the structure is better than that of only previously known model. Particularly, a catalytic triad was clearly identified, in agreement with the experimental information available. Analysis of intermediates in the enzymatic mechanism led to the identification of key residues for substrate binding, stereoselectivity, and intermediate stabilization during the reaction. In particular, we have confirmed the role of the oxyanion hole and the conserved motif (HGXP) in epoxide hydrolases, in excellent agreement with known experimental and computational data on similar systems. The model obtained is the first one that fully agrees with all the experimental observations on the system. (C) 2017 Wiley Periodicals, Inc.

Ämnesord

NATURVETENSKAP  -- Kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

NATURVETENSKAP  -- Data- och informationsvetenskap -- Bioinformatik (hsv//swe)

NATURAL SCIENCES  -- Computer and Information Sciences -- Bioinformatics (hsv//eng)

Nyckelord

microsomal epoxide hydrolase

homology models

clustering

ensemble-based docking

epilepsy

agrobacterium-radiobacter ad1

particle mesh ewald

aspergillus-niger

catalyzed-hydrolysis

reaction-mechanism

hypersensitivity reactions

force-field

enantioselectivity

carbamazepine

quality

Biochemistry & Molecular Biology

Biophysics

clustering

Biology

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