title: Targeting of AMP-activated protein kinase: prospects for computer-aided drug design.
abstract: Dysregulation of energy homeostasis has been implicated in a number of human chronic diseases including diabetes, obesity, cancer, and inflammation. Given the functional attributes as a central regulator of energy homeostasis, AMP-activated protein kinase (AMPK) is emerging as a therapeutic target for these diseases, and lines of evidence have highlighted the need for rational and robust screening systems for identifying specific AMPK modulators with a therapeutic potential for preventing and/or curing these diseases. Areas covered: Here, the authors review the recent advances in the understanding of three-dimensional structures of AMPK in relationship with the regulatory mechanisms, potentials of AMPK as a therapeutic target in human chronic diseases, and prospects of computer-based drug design for AMPK. Expert opinion: Accumulating information of AMPK structure has provided us with deep insight into the molecular basis underlying the regulatory mechanisms, and further discloses several structural domains, which can be served for a target site for computer-based drug design. Molecular docking and simulations provides useful information about the binding sites between potent drugs and AMPK as well as a rational screening format to discover isoform-specific AMPK modulators. For these reasons, the authors suggest that computer-aided virtual screening methods hold promise as a rational approach for discovering more specific AMPK modulators.
authors: a Department of Oral Biochemistry and Molecular Biology, School of Dentistry , Kyung Hee University , Dongdaemun-gu , Republic of Korea.
authors: Joungmok
authors: J
authors: Kim
authors: b Department of Biochemistry and Molecular Biology, Graduate School , Kyung Hee University , Seoul , Republic of Korea.
authors: Goowon
authors: G
authors: Yang
authors: b Department of Biochemistry and Molecular Biology, Graduate School , Kyung Hee University , Seoul , Republic of Korea.
authors: Joohun
authors: J
authors: Ha
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D003198:Computer Simulation; D017076:Computer-Aided Design; D015195:Drug Design; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy
chemical_list: D055372:AMP-Activated Protein Kinases
keywords: AMPK; AMPK modulator; cancer; computer-aided screening; diabetes; obesity