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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.
Molecular docking and molecular dynamics methods were used to study the effect of dimethylarginine dimethylamine hydrolase-1 (DDAH-1) and its inhibitor, l-VNIO and imine L-Ornithine (Me-L-Ornithine) (Me-L-NIO) interaction and binding mode, and based on the experimental results obtained iminophenethyl- The results showed that the inhibitory effect of L-VNIO on DDAH-1 was stronger than that of Me-L-NIO, and the result was in good agreement with the experimentally measured values of IC50 of semi-inhibitory concentration of L-VNIO and Me-L-NIO on DDAH-1 The five amino acid residues of Phe75, Asp78, His172, Ser175 and Asp268 play a very important role in the complexes formed by the three inhibitors. From the results of the calculation, we deduced that among the three inhibitors we designed Ph-L-NIO has the best inhibitory effect on DDAH-1.