Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV). Antiretroviral therapy (ART) against HIV infection offers the promise of controlling disease progression and prolonging the survival of HIV-infected patients. Reverse transcriptase (RT) inhibitors remain the cornerstone of the drug regimen to treat AIDS. In this direction, by using group-based QSAR study (G-QSAR), identification of the structural need for the development of lead structure with reverse transcriptase inhibition on 97 reported structures was carried out. Docking analysis was performed further and suggested the structural properties required for binding affinity with the receptor. The molecules in the data set were fragmented into six (R1, R2, R3, R4, R5, and R6) by applying the fragmentation pattern. Three G-QSAR models were selected based on the statistical significance of the model. The molecular docking study was performed to explain the structural properties required for the design of potent HIV-RT inhibitors. The statistically validated QSAR models reveal the presence of higher hydrophobic groups containing single-bonded –Br atom, 2 aromatic bonded –NH group with less electronegativity, and entropic interaction fields at R2 essential for better anti-HIV activity. The presence of a lipophilic group at R3, oxygen and sulfur connected with two aromatic bonds at R4, and –CH3 group at R5 was fruitful for reverse transcriptase inhibition. Docking studies of the selected inhibitors with the active site of reverse transcriptase enzyme showed hydrogen bond, Van der Waal’s, charge, aromatic, and π–π interactions with residues present at the active site. The results of the generated models provide significant site-specific insight into the structural requirements for reverse transcriptase inhibition during the design and development of novel anti-HIV compounds. Molecular docking study revealed the binding interaction between the ligand and the receptor which gave insight towards the structure-based design for the discovery of more potent compounds with better activity against HIV infection.

中文翻译：

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通过 G-QSAR 和 4-芳硫基和 4-芳氧基-3-碘吡啶-2(1-H)-one 衍生物的分子对接研究，合理设计 HIV-RT 抑制剂的计算机药物

人类免疫缺陷病毒感染和获得性免疫缺陷综合征 (HIV/AIDS) 是由人类免疫缺陷病毒 (HIV) 感染引起的一系列疾病。针对 HIV 感染的抗逆转录病毒疗法 (ART) 有望控制疾病进展并延长 HIV 感染患者的生存期。逆转录酶 (RT) 抑制剂仍然是治疗 AIDS 药物方案的基石。在这个方向上，通过使用基于组的 QSAR 研究 (G-QSAR)，确定了对 97 个报告结构进行逆转录酶抑制的先导结构开发的结构需求。进一步进行对接分析并提出与受体结合亲和力所需的结构特性。数据集中的分子被分成六个（R1、R2、R3、R4、R5、和 R6) 通过应用碎片模式。根据模型的统计显着性选择了三个G-QSAR模型。进行分子对接研究是为了解释设计有效的 HIV-RT 抑制剂所需的结构特性。经统计验证的 QSAR 模型显示，存在含有单键 -Br 原子的更高疏水基团、电负性较低的 2 个芳香键 -NH 基团，以及 R2 处的熵相互作用场，这对于更好的抗 HIV 活性至关重要。R3 处存在亲脂基团，R4 处与两个芳香键相连的氧和硫，以及 R5 处的 –CH3 基团对逆转录酶抑制是卓有成效的。所选抑制剂与逆转录酶活性位点的对接研究显示氢键、范德华、电荷、芳香、和 π-π 与活性位点上的残基相互作用。生成的模型的结果为在设计和开发新型抗 HIV 化合物期间对逆转录酶抑制的结构要求提供了重要的位点特异性洞察。分子对接研究揭示了配体和受体之间的结合相互作用，这为基于结构的设计提供了见解，以发现对 HIV 感染具有更好活性的更有效化合物。