Homology Modeling and Ligand Docking of Mitogen-activated Protein Kinase-activated Protein Kinase 5 (MK5)

Overview

Journal Theor Biol Med Model

Publisher Biomed Central

Date 2013 Sep 17

PMID 24034446

Citations 4

Authors

Inger Lindin

Yimingjiang Wuxiuer

Irina Kufareva

Ruben Abagyan

Ugo Moens

Ingebrigt Sylte

Aina Westrheim Ravna

Affiliations

Soon will be listed here.

Abstract

Background: Mitogen-activated protein kinase-activated protein kinase 5 (MK5) is involved in one of the major signaling pathways in cells, the mitogen-activated protein kinase pathway. MK5 was discovered in 1998 by the groups of Houng Ni and Ligou New, and was found to be highly conserved throughout the vertebrates. Studies, both in vivo and in vitro, have shown that it is implicated in tumor suppression as well as tumor promotion, embryogenesis, anxiety, locomotion, cell motility and cell cycle regulation.

Methods: In order to obtain a molecular model of MK5 that can be used as a working tool for development of chemical probes, three MK5 models were constructed and refined based on three different known crystal structures of the closely related MKs; MK2 [PDB: 2OZA and PDB: 3M2W] and MK3 [PDB: 3FHR]. The main purpose of the present MK5 molecular modeling study was to identify the best suited template for making a MK5 model. The ability of the generated models to effectively discriminate between known inhibitors and decoys was analyzed using receiver operating characteristic (ROC) curves.

Results: According to the ROC curve analyzes, the refined model based on 3FHR was most effective in discrimination between known inhibitors and decoys.

Conclusions: The 3FHR-based MK5 model may serve as a working tool for development of chemical probes using computer aided drug design. The biological function of MK5 still remains elusive, but its role as a possible drug target may be elucidated in the near future.

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