二甲基精氨酸二甲胺水解酶-1的理论研究

运用分子对接和分子动力学方法研究二甲基精氨酸二甲胺水解酶-1(DDAH-1)与其抑制剂亚胺基烯丁基-L-鸟氨酸(L-VNIO)和亚胺基丙基-L-鸟氨酸(Me-L-NIO)的相互作用和结合模式,并根据实验得到的结论设计了亚胺基苯乙基-L-鸟氨酸(Ph-L-NIO)抑制剂.结果表明:L-VNIO比Me-L-NIO对DDAH-1的抑制效果更强,这个结果与实验测得L-VNIO和Me-L-NIO对DDAH-1的半抑制浓度IC50值大小一致.Phe75、Asp78、His172、Ser175和Asp268这五个氨基酸残基在三种抑制剂形成的复合物中起到非常重要的作用,从计算结果推断在这三个抑制剂中我们设计得到的Ph-L-NIO对DDAH-1的抑制效果最好.

Theoretical studies on dimethylarginine dimethylaminohydrolase-1

The interaction and combination mode of N^ω,N^ω-dimethyl-L-arginine dimethylaminohydrolase-1 （DDAH-1） and its inhibitors N^5-（1-iminobut-3-enyl）-L-ornithine（L-VNIO） and N^5-（1-iminopropyl）-L-ornithine（Me-L-NIO） were studied by using the methods of molecular docking and molecular dynamics,and N5-（1-iminobut-3-phenyl）-L-ornithine（Ph-L-NIO） inhibitor is designed according to the experimental results. The result shows that the combination of L-VNIO with DDAH-1 is stronger than Me-L-NIO,which reflects the experimental inhibitory activity expressed in terms of the half maximal inhibitory concentration （the IC50value）. Phe75、Asp78、His172、Ser175 and Asp268 play very important role in the compound formed by the three kinds of inhibitors and form the results that N5-（1-iminobut-3-phenyl）-L-ornithine（Ph-L-NIO） could most effectively inhibit DDAH-1.