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Progress in Chemistry 2010, Vol. 22 Issue (05): 993-1001 Previous Articles   Next Articles

Special Issue: 计算化学

• Invited Article •

Computational Chemistry of Protein Kinase A and Its Inhibitor Balanol

Jin Haixiao; Yan Xiaojun**; Zhu Peng   

  1. (Key Laboratory of Marine Biotechnology, Ningbo University, Ningbo 315211, China)
  • Received: Revised: Online: Published:
  • Contact: Yan Xiaojun E-mail:yanxiaojun@nbu.edu.cn
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Protein kinases regulate signal transduction pathways in cell by phosphorylating the protein kinase substrate, and they are important targets in drug design. Protein kinase A (PKA) is the first kinase that was obtained X-ray structure of its catalytic domain, and is regarded as prototype for protein kinase superfamily. The progress in computational chemistry study of protein kinase A has been reviewed, including the molecular dynamics simulation study of PKA holoenzyme and its C subunit and R subunit in aqueous solution, phosphoryl transfer mechanism, the binding free energy predicting and flexible docking of C subunit with its inhibitor balanol. Various computational approaches are applied to this system, including molecular dynamics simulation, dock, homology modeling, QM/MM.

Contents
1 Introduction
2 Molecular dynamics simulation study on PKA
2.1 Molecular dynamics simulation study on C subunit
2.2 Modeling of the complex of C subunit and R subunit
2.3 Molecular dynamics simulation study on R subunit
3 Phosphoryl transfer mechanism
4 Balanol
4.1 Prediction of binding free energy
4.2 Flexible protein-flexible ligand docking
4.3 Mechanism of high selectivity of balanol analogue BD2
4.4 Functional role of structure water molecules in the recognition of C subunit and BD2
5 Conclusion and outlook

Key words: protein kinase A (PKA), balanol, molecular dynamics simulation, dock, QM/MM

CLC Number: 

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