Homology modeling, molecular dynamic simulation and docking studies of cyclin dependent kinase 1.
In order to develop promising cyclin dependent kinase 1 inhibitors, homology modeling, docking and molecular dynamic simulation techniques were applied to get insight into the functional and structural properties of cyclin dependent kinase 1 (CDK1). Since there is no reported CDK1 crystal structural data, the three dimensional structure of CDK1 was constructed based on homology modeling. An extensive dynamic simulation was also performed on a Flavopiridol-CDK1 complex for probing the binding pattern of Flavopiridol in the active site of CDK1. The binding modes of other inhibitors to CDK1 were also proposed by molecular docking. The structural requirement for developing more potent CDK1 inhibitors was obtained by the above-mentioned molecular simulations and pharmacophore modeling.
Zhang
Lei
L
Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Jinan, Shandong, China.
Zhu
Huawei
H
Wang
Qiang
Q
Fang
Hao
H
Xu
Wenfang
W
Li
Minyong
M
D000595:Amino Acid Sequence; D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D003198:Computer Simulation; D005419:Flavonoids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008956:Models, Chemical; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D005419:Flavonoids; D010880:Piperidines; D047428:Protein Kinase Inhibitors; C077990:alvocidib; D016203:CDC2 Protein Kinase