Molecular Mechanism Studies on Interactions Between Adenylosuccinate Synthetase and Its Inhibitors

作者：Wang Yue Peng; Wang Ming An; Du Feng Pei; Li Xiang Dong; Yao Guang Wei; Zhang Pan Dan; Lu Hui Zhe^*

来源：Chemical Journal of Chinese Universities, 2010, 31(2): 336-342.

• Adenylosuccinate synthetase(AdSS)
• Inhibitor
• Molecule docking
• Density functional theory

By density functional theory B3LYP method with 6-31G(d) basis set, the geometry and electronic structure of the natural inhibitor and derivatives of Adenylosuccinate synthetase (AdSS) were optimized and their thermodynamic stability was also analyzed. The. relationship between their electronic structures and bioactivities were discussed based on the Mulliken bond order, atomic net charge distribution and molecular surface electrostatic potential. According to the complex structure of AdSS and its substrate IMP as well as the optimized stable conformation of natural Inhibitors, the interaction mode between AdSS and its inhibitors was studied with molecular docking, mechanical optimization and molecular dynamics simulation methods. These results show that the phosphate group and the hydantoin ring of the inhibitors form the pharmacophore model. The van der Waals energy played more important role in binding compared with the electrostatic energy. Furthermore, the inhibitors were mainly located in the hydrophobic cavity of the AdSS.

• 出版日期2010-2-10
• 单位中国农业大学