Study on the hydrolysis mechanism of phosphodiesterase 4 using molecular dynamics simulations

被引:9
作者
Kang, N. S. [1 ]
Chae, C. H. [1 ]
Yoo, S. -E. [1 ]
机构
[1] Korea Res Inst Chem Technol, Taejon 305343, South Korea
关键词
PDE4; cAMP; molecular dynamics simulation; hydrolysis mechanism; hydration pattern;
D O I
10.1080/08927020600717111
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
We carried out NPT molecular dynamics simulations in an explicit solvent to better understand the mechanism of cyclic adenosine monophosphates (cAMP) hydrolysis by phosphodiesterase 4 (PDE4) enzyme on atomic details and to obtain information on the dynamics characteristic of the catalytic domains of PDE4. In analyzing the water hydrogen-bond network around the active site, we also showed the importance of water in drug-protein interactions. In addition, we reported the characteristics of the hydration pattern and the dynamic distance distribution around the interesting residues. The results indicated that Asp318 plays the role of a general base that can activate water molecule for nucleophilic attack on cAMP. As expected, His160 plays the role of a proton donor for cAMP.
引用
收藏
页码:369 / 374
页数:6
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