Exploring the Ligand Recognition Properties of the Human Vasopressin V1a Receptor Using QSAR and Molecular Modeling Studies
Exploring the Ligand Recognition Properties of the Human Vasopressin V1a Receptor Using QSAR and Molecular Modeling Studies
复制标题
DOI：
10.1111/cbdd.12229
复制
发表时间：
2014-02-01
影响因子：
3
通讯作者：
Correa-Basurto, Jose
中科院分区：
文献类型：
--
作者：
Contreras-Romo, Martha C.;Martinez-Archundia, Marlet;Correa-Basurto, Jose
伐普坦是作为非肽加压素受体拮抗剂的化合物。这些化合物具有不同的化学结构。在这项研究中，我们使用了蛋白质折叠、分子动力学模拟、对接和定量构效关系（QSAR）的综合方法来阐明加压素受体V1 a（V1 aR）与其一些阻断剂的详细相互作用（134）。定量构效关系的研究进行了MLR分析，并被聚集到一个组进行人工神经网络（ANN）分析。对于每个分子，计算了1481个分子描述符。此外，计算了15个量子化学描述符。在去除离群值后，通过选择描述符的最佳组合来开发最终方程。分子建模使我们能够获得一个可靠的三维模型V1 aR。对接结果表明，绝大多数的配体到达结合位点下，-，-阳离子和疏水相互作用。定量构效关系研究表明，杂原子N和O是重要的配体识别，这可以解释的配体的结构多样性，达到V1 aR。
Vaptans are compounds that act as non-peptide vasopressin receptor antagonists. These compounds have diverse chemical structures. In this study, we used a combined approach of protein folding, molecular dynamics simulations, docking, and quantitative structure-activity relationship (QSAR) to elucidate the detailed interaction of the vasopressin receptor V1a (V1aR) with some of its blockers (134). QSAR studies were performed using MLR analysis and were gathered into one group to perform an artificial neural network (ANN) analysis. For each molecule, 1481 molecular descriptors were calculated. Additionally, 15 quantum chemical descriptors were calculated. The final equation was developed by choosing the optimal combination of descriptors after removing the outliers. Molecular modeling enabled us to obtain a reliable tridimensional model of V1aR. The docking results indicated that the great majority of ligands reach the binding site under -, -cation, and hydrophobic interactions. The QSAR studies demonstrated that the heteroatoms N and O are important for ligand recognition, which could explain the structural diversity of ligands that reach V1aR.