Informatics, GVK Biosciences Private Limited, 37 Sterling Road, Chennai 600034, Tamil Nadu, India.
Eur J Med Chem. 2011 Mar;46(3):851-9. doi: 10.1016/j.ejmech.2010.12.022. Epub 2011 Jan 9.
The purpose of this study is to identify novel and potent inhibitors against HIV-1 reverse transcriptase (RT). The crystal structure of the most active ligand was converted into a feature-shaped query. This query was used to align molecules to generate statistically valid 3D-QSAR (r(2) = 0.873) and Pharmacophore models (HypoGen). The best HypoGen model consists of three Pharmacophore features (one hydrogen bond acceptor, one hydrophobic aliphatic and one ring aromatic) and further validated using known RT inhibitors. The designed novel inhibitors are further subjected to docking studies to reduce the number of false positives. We have identified and proposed some novel and potential lead molecules as reverse transcriptase inhibitors using analog and structure based studies.
本研究旨在寻找新型、有效的 HIV-1 逆转录酶（RT）抑制剂。将最活跃配体的晶体结构转化为特征形状查询。该查询用于对齐分子，以生成具有统计学意义的 3D-QSAR（r(2) = 0.873）和药效团模型（HypoGen）。最佳 HypoGen 模型由三个药效团特征（一个氢键受体、一个疏水性脂肪族和一个环状芳香族）组成，并使用已知的 RT 抑制剂进一步验证。设计的新型抑制剂进一步进行对接研究，以减少假阳性。我们通过类似物和基于结构的研究，确定并提出了一些新型的、有潜力的潜在先导分子作为逆转录酶抑制剂。
