3D-QSAR modeling of Phosphodiesterase-5 inhibitors: evaluation and comparison of the receptor- and ligand-based alignments
3D-QSAR modeling of Phosphodiesterase-5 inhibitors: evaluation and comparison of the receptor- and ligand-based alignments
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磷酸二酯酶 5 抑制剂的 3D-QSAR 建模：基于受体和配体的比对的评估和比较
DOI：
10.1007/s00044-019-02311-x
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发表时间：
2019-06
影响因子：
2.6
通讯作者：
Cai Xiong
中科院分区：
文献类型：
--
作者：
Jiang Zan;Zheng Xuehua;Li Zhong;Pan Shuqiong;Wang Xiaoyu;Zhang Chen;Li Zhe;Luo Hai Bin;Wu Deyan;Cai Xiong
磷酸二酯酶-5(PDE5)抑制剂可作为治疗勃起功能障碍和肺动脉高压的临床药物。一系列芳基-色烯-吡咯衍生物已被本实验室鉴定为PDE5抑制剂。在此，我们用CoMFA和CoMSIA方法对这些分子进行了3D-QSAR分析，以更深入地了解它们的生物活性的结构要求。使用基于受体和配体的比对方法并进行比较，以找出影响QSAR模型准确性的比对相关因素。基于受体的CoMFA和CoMSIA模型是通过将对接构象直接叠加在蛋白质结合部位而产生的，对38个训练集化合物和5个测试集分子给出了更显著的结果。两种比对结果的比较表明，配体的空间排列是决定3D-QSAR模型可靠性的主要因素。对基于受体的CoMSIA-SE等值线图的详细分析为提高芳基-色烯-吡咯类似物作为PDE5抑制剂的生物活性提供了许多有用的信息。
Phosphodiesterase-5 (PDE5) inhibitors can be used as clinical agents for the treatment of erectile dysfunction and pulmonary hypertension. A series of aryl-chromeno-pyrrol derivatives were previously identified as PDE5 inhibitors in our lab. Herein, these molecules were subjected to 3D-QSAR analysis with CoMFA and CoMSIA methods to gain deeper insight into the structural requirements for their bioactivities. Receptor- and ligand-based alignment were used and compared to find the alignment-related factors that affect the accuracy of QSAR models. The receptor-based CoMFA and CoMSIA models, which were generated by superimposing the docking conformations directly in the protein binding site, gave more significant results for 38 training set compounds and 5 test set molecules. Comparison of the two alignments revealed that spatial arrangement of the ligands is the principal factor in determining the reliability of the 3D-QSAR models. Detailed analysis of the receptor-based CoMSIA-SE contour maps provided much helpful information to improve the bioactivities of aryl-chromeno-pyrrol analogs as PDE5 inhibitors.
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影响因子：
6.7
作者：
T. Oh;K. Kang;B. Ahn;M. Yoo;W. Kim
通讯作者：
T. Oh;K. Kang;B. Ahn;M. Yoo;W. Kim
影响因子：
2.8
作者：
H. Porst
通讯作者：
H. Porst
影响因子：
4.3
作者：
Dioma U. Udeoji;E. Schwarz
通讯作者：
Dioma U. Udeoji;E. Schwarz
3-(3,4-二氢异喹啉-2(1H)-基磺酰基)苯甲酸作为 AKR1C3 抑制剂的 3D-QSAR 研究：强调分子对接在构象生成中的重要性
影响因子：
2.7
作者：
Xuehua Zheng;Yinuo Wu;Deyan Wu;Xinhua Wang;Chao Zhang;Xiaolei Guo;Hai-Bin Luo
通讯作者：
Hai-Bin Luo
影响因子：
158.5
作者：
Galiè, N;Ghofrani, HA;Simonneau, G
通讯作者：
Simonneau, G