Paneth Agata, Płonka Wojciech, Paneth Piotr
Faculty of Pharmacy with Medical Analytics Division, Medical University of Lublin, Chodźki 4a, 20-093, Lublin, Poland.
FQS-Fujitsu Poland, Parkowa 11, 33-332 Kraków, Poland.
Pharmaceuticals (Basel). 2019 Apr 24;12(2):64. doi: 10.3390/ph12020064.
In this study, 48 inhibitors were docked to 107 allosteric centers of human immunodeficiency virus 1 (HIV-1) reverse transcriptase from the Protein Data Bank (PDB). Based on the average binding scores, quantitative structure-activity relationship (QSAR) equations were constructed in order to elucidate directions of further development in the design of inhibitors. Such developments, informed by structural data, must have a focus on activity against mutated forms of the enzyme, which are the cause of the emergence of multidrug-resistant viral strains. Docking studies employed the HYDE scoring function. Two types of QSARs have been considered: One based on topological descriptors and the other on structural fragments of the inhibitors. Both methods gave similar results, indicating substructures favoring binding to mutated forms of the enzyme.
在本研究中，从蛋白质数据库（PDB）获取了48种抑制剂，并将其与人类免疫缺陷病毒1（HIV-1）逆转录酶的107个变构中心进行对接。基于平均结合分数，构建了定量构效关系（QSAR）方程，以阐明抑制剂设计的进一步发展方向。这种基于结构数据的发展，必须专注于针对该酶突变形式的活性，而这些突变形式是多药耐药病毒株出现的原因。对接研究采用了HYDE评分函数。考虑了两种类型的QSAR：一种基于拓扑描述符，另一种基于抑制剂的结构片段。两种方法都得到了相似的结果，表明存在有利于与该酶突变形式结合的亚结构。
