Journal article
(Original article)


Structural insight into the prolyl hydroxylase PHD2: A molecular dynamics and DFT study


Publication Details
Author(s): Wick C, Lanig H, Jäger C, Burzlaff N, Clark T
Publisher: Wiley-VCH Verlag
Publication year: 2012
Journal issue: 31
Pages range: 4973-4985
ISSN: 1434-1948
Language: English

Abstract

We describe computational studies of the mode of action of the prolyl hydroxylase domain containing protein (PHD2). Long-term molecular dynamics (MD) simulations were performed to investigate the rigidity of the crystallographically observed conformations of PHD2 in solution. We also describe the influence of the C-terminal oxygen-dependent degradation domain (CODD) of hypoxia inducible factor 1α (HIF-1α) on the overall behaviour of the protein, including the effect of the natural ligand 2-oxoglutarate (2OG) and an isoquinoline inhibitor. To study the geometry of the 2-His-1-carboxylate facial triad and its dependency on the protein environment, we performed DFT calculations on model systems and compared them with quantum mechanics/molecular mechanics (QM/MM) gas-phase energy minimisations, which allowed us to treat the whole protein. The combination of these methods provides insight into the behaviour of the 2-His-1-carboxylate facial triad with 2OG and an inhibitor of PHD2 on the atomistic scale. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.



How to cite
APA: Wick, C., Lanig, H., Jäger, C., Burzlaff, N., & Clark, T. (2012). Structural insight into the prolyl hydroxylase PHD2: A molecular dynamics and DFT study. European Journal of Inorganic Chemistry, 31, 4973-4985. https://dx.doi.org/10.1002/ejic.201200391

MLA: Wick, Christian, et al. "Structural insight into the prolyl hydroxylase PHD2: A molecular dynamics and DFT study." European Journal of Inorganic Chemistry 31 (2012): 4973-4985.

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