In silico profiling the interaction mechanism of 2,5-diketopiperazine derivatives as oxytocin antagonists

Publication date: Available online 16 March 2019Source: Journal of Molecular Graphics and ModellingAuthor(s): Ming Yang, Jianghe Luo, Zhumei Zeng, Ling Yang, Limian Xu, Yan LiAbstractOxytocin plays a vital role in the occurrence of preterm birth by interacting with oxytocin receptor (OTR), and thus OTR antagonists provide effective approaches for the treatment of early birth. Presently, for purpose of exploring the structural traits affecting the antagonism potency, the up-to-date largest set of 121 2,5-diketopiperazine derivatives as OTR antagonists was subjected to ligand-based three-dimensional quantitative structure–activity (3D-QSAR) analysis applying comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The resultant optimal CoMSIA model displays proper validity and predictability with cross-validated correlation coefficient Q2 = 0.614, non-cross-validated correlation coefficient R2ncv = 0.969 and predicted correlation coefficient R2pre = 0.912 for the test set of compounds, respectively. In addition, docking study was carried out for further elucidating the binding modes of OTR antagonists. The final docking cavity was located among the TM2-TM7 helices of the target protein and proved to be the same as described by other scholars' researches of other type of OTR antagonists. The major amino acids forming the cavity are Q92, Q96, K116, Q119, V120, M123, G196, I201, Q295, W288, F311 and M315. Re...
Source: Journal of Molecular Graphics and Modelling - Category: Molecular Biology Source Type: research