Virtual screening for anti-HIV-1 RT and anti-HIV-1 PR inhibitors from the Thai medicinal plants database: A combined docking with neural networks approach
Virtual screening for anti-HIV-1 RT and anti-HIV-1 PR inhibitors from the Thai medicinal plants database: A combined docking with neural networks approach
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DOI：
10.2174/1386207054546469
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发表时间：
2005-08-01
影响因子：
1.8
通讯作者：
Hannongbua, S
中科院分区：
文献类型：
--
作者：
Sangma, C;Chuakheaw, D;Hannongbua, S
将小分子对接到已知蛋白质结构中的虚拟筛选方法是药物设计的有力工具。在这项工作中，结合对接和神经网络的方法，使用自组织映射，已开发并应用于筛选抗HIV-1抑制剂的两个目标，HIV-1 RT和HIV-1 PR，从泰国药用植物数据库中的活性化合物。基于奈韦拉平和calanlavine A作为HIV-1 RT结合位点的参考结构以及HIV-1 PR结合位点的XK-263，数据库中的2，684种化合物被对接到靶酶中。自组织地图，然后生成相对于三种类型的药效组。然后将参考结构图叠加在所有筛选化合物的特征图上。仅接受与参比化合物具有相似特征的结构。通过使用SOM，HIV-1 RT的候选化合物数量减少到6种和9种，分别与奈韦拉平和卡兰布曲明A一致，作为参考。对于HIV-1 PR靶点，有135个筛选的化合物显示出与XK-263特征图谱良好的一致性。将进一步测试这些筛选的化合物的HIV-1抑制亲和力。结果表明，该方法能有效地减少AutoDock和评分过程中的分析步骤，有利于后续筛选。
The virtual screening approach for docking small molecules into a known protein structure is a powerful tool for drug design. In this work, a combined docking and neural network approach, using a self-organizing map, has been developed and applied to screen anti-HIV-1 inhibitors for two targets, HIV-1 RT and HIV-1 PR, from active compounds available in the Thai Medicinal Plants Database. Based on nevirapine and calanolide A as reference structures in the HIV-1 RT binding site and XK-263 in the HIV-1 PR binding site, 2,684 compounds in the database were docked into the target enzymes. Self-organizing maps were then generated with respect to three types of pharmacophoric groups. The map of the reference structures were then superimposed on the feature maps of all screened compounds. Only the structures having similar features to the reference compounds were accepted. By using the SOMs, the number of candidates for HIV-1 RT was reduced to six and nine compounds consistent with nevirapine and calanolide A, respectively, as references. For the HIV-1 PR target, there are 135 screened compounds showed good agreement with the XK-263 feature map. These screened compounds will be further tested for their HIV-1 inhibitory affinities. The obtained results indicate that this combined method is clearly helpful to perform the successive screening and to reduce the analyzing step from AutoDock and scoring procedure.