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Int. J. Mol. Sci. 2014, 15(3), 4878-4902; doi:10.3390/ijms15034878
Article

Comparative Molecular Dynamics Simulations of Mitogen-Activated Protein Kinase-Activated Protein Kinase 5

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Received: 19 December 2013; in revised form: 21 February 2014 / Accepted: 28 February 2014 / Published: 19 March 2014
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Abstract: The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ERK3 and ERK4. Cell culture and animal studies have demonstrated that MK5 is involved in tumour suppression and promotion, embryogenesis, anxiety, cell motility and cell cycle regulation. In the present study, homology models of MK5 were used for molecular dynamics (MD) simulations of: (1) MK5 alone; (2) MK5 in complex with an inhibitor; and (3) MK5 in complex with the interaction partner p38α. The calculations showed that the inhibitor occupied the active site and disrupted the intramolecular network of amino acids. However, intramolecular interactions consistent with an inactive protein kinase fold were not formed. MD with p38α showed that not only the p38 docking region, but also amino acids in the activation segment, αH helix, P-loop, regulatory phosphorylation region and the C-terminal of MK5 may be involved in forming a very stable MK5-p38α complex, and that p38α binding decreases the residual fluctuation of the MK5 model. Electrostatic Potential Surface (EPS) calculations of MK5 and p38α showed that electrostatic interactions are important for recognition and binding.
Keywords: MAPKAPK5; MK5; PRAK; homology modelling; protein-ligand complexes; p38α; protein-protein interactions; molecular dynamics simulations; molecular mechanisms; electrostatic potential surfaces MAPKAPK5; MK5; PRAK; homology modelling; protein-ligand complexes; p38α; protein-protein interactions; molecular dynamics simulations; molecular mechanisms; electrostatic potential surfaces
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Lindin, I.; Wuxiuer, Y.; Ravna, A.W.; Moens, U.; Sylte, I. Comparative Molecular Dynamics Simulations of Mitogen-Activated Protein Kinase-Activated Protein Kinase 5. Int. J. Mol. Sci. 2014, 15, 4878-4902.

AMA Style

Lindin I, Wuxiuer Y, Ravna AW, Moens U, Sylte I. Comparative Molecular Dynamics Simulations of Mitogen-Activated Protein Kinase-Activated Protein Kinase 5. International Journal of Molecular Sciences. 2014; 15(3):4878-4902.

Chicago/Turabian Style

Lindin, Inger; Wuxiuer, Yimingjiang; Ravna, Aina W.; Moens, Ugo; Sylte, Ingebrigt. 2014. "Comparative Molecular Dynamics Simulations of Mitogen-Activated Protein Kinase-Activated Protein Kinase 5." Int. J. Mol. Sci. 15, no. 3: 4878-4902.



Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert