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论文类型：期刊论文

发表时间：2014-09-25

发表刊物：JOURNAL OF MOLECULAR STRUCTURE

收录刊物：SCIE、EI、Scopus

卷号：1074

页面范围：294-301

ISSN号：0022-2860

关键字：Migraine; CGRP receptor antagonist; 3D-QSAR; Molecular docking

摘要：The migraine never fails to afflict individuals in the world that knows no lack of such cases. CGRP (calcitonin gene-related peptide) is found closely related to migraine and olcegepant (BIBN4096) is effective in alleviating the pain. In our work, the combination of ligand- and receptor-based three-dimensional quantitative structure-activity relationship (3D-QSAR) studies along with molecular docking was applied to provide us insights about how urethanamide, pyridine and aspartate and succinate derivatives (novel CGRP receptor antagonists) play a part in inhibiting the activity of CGRP receptor. The optimal CoMSIA model shows the Q(2) of 0.505, R-ncv(2) of 0.992 and its accurate predictive ability was confirmed by checking out an independent test set which gave R-pred(2) value of 0.885. Besides, the 3D contour maps help us identify how different groups affect the antagonist activity while connecting to some key positions. In addition, the docking analysis shows the binding site emerging as the distorted "V" shape and including two binding pockets: one of them is hydrophobic, fixing the structural part 3 of compound 80, the other anchors the part 1 of compound 80. The docking analysis also shows the interaction mechanism between