Background: Mitogen-activated protein kinase-activated protein kinase 5 (MK5) is\r\ninvolved in one of the major signaling pathways in cells, the mitogen-activated\r\nprotein kinase pathway. MK5 was discovered in 1998 by the groups of Houng Ni\r\nand Ligou New, and was found to be highly conserved throughout the vertebrates.\r\nStudies, both in vivo and in vitro, have shown that it is implicated in tumor\r\nsuppression as well as tumor promotion, embryogenesis, anxiety, locomotion,\r\ncell motility and cell cycle regulation.\r\nMethods: In order to obtain a molecular model of MK5 that can be used as a\r\nworking tool for development of chemical probes, three MK5 models were\r\nconstructed and refined based on three different known crystal structures of the\r\nclosely related MKs; MK2 [PDB: 2OZA and PDB: 3M2W] and MK3 [PDB: 3FHR]. The\r\nmain purpose of the present MK5 molecular modeling study was to identify the best\r\nsuited template for making a MK5 model. The ability of the generated models to\r\neffectively discriminate between known inhibitors and decoys was analyzed using\r\nreceiver operating characteristic (ROC) curves.\r\nResults: According to the ROC curve analyzes, the refined model based on 3FHR\r\nwas most effective in discrimination between known inhibitors and decoys.\r\nConclusions: The 3FHR-based MK5 model may serve as a working tool for\r\ndevelopment of chemical probes using computer aided drug design. The biological\r\nfunction of MK5 still remains elusive, but its role as a possible drug target may be\r\nelucidated in the near future.
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