点击次数：

论文类型：期刊论文

发表时间：2016-07-27

发表刊物：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录刊物：SCIE、EI、Scopus

卷号：64

期号：29

页面范围：5941-5950

ISSN号：0021-8561

关键字：BVDV RdRp; 3D-QSAR; docking; molecular dynamics; MM-PBSA

摘要：Bovine viral diarrhea virus (BVDV) infections are prevailing in cattle populations on a worldwide scale. The BVDV RNA-dependent RNA polymerase (RdRp), as a promising target for new anti-BVDV drug development, has attracted increasing attention. To explore the interaction mechanism of 65 benzimidazole scaffold-based derivatives as BVDV inhibitors, presently, a computational study was performed based on a combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations. The resultant optimum CoMFA and CoMSIA models present proper reliabilities and strong predictive abilities (with Q(2) = 0.64, R-ncv(2) = 0.93, R-pred(2) = 0.80 and Q(2) = 0.65, R-ncv(2) = 0.98, R-pred(2) = 0.86, respectively). In addition, there was good concordance between these models, molecular docking, and MD results. Moreover, the MM-PBSA energy analysis reveals that the major driving force for ligand binding is the polar solvation contribution term. Hopefully, these models and the obtained findings could offer better understanding of the interaction mechanism of BVDV inhibitors as well as benefit the new discovery of more potent BVDV inhibitors.