Key Laboratory of Arable Land Conservation (Middle and Lower Reaches of Yangtse River), Ministry of Agriculture, College of Resources and Environment, Huazhong Agricultural University, Wuhan 430070, China.
Environ Toxicol Pharmacol. 2013 Mar;35(2):228-34. doi: 10.1016/j.etap.2012.11.018. Epub 2012 Dec 21.
By using multi-block partial least-squares (MBPLS) method, quantitative structure-activity relationship (QSAR) between 35 organophosphate compounds (OP) and their 24h acute toxicities towards the housefly (Musca nebulo L.) was built on the molecular interaction fields (MIF) descriptors, which were obtained with O, N and DRY as probes, and then normalised with block unscaled weights (BUW) technique. The best QSAR model had 8 principal components, with the coefficient of determination R(2)=0.995 and that of leave-one-out cross-validation Q(2)=0.865, and the corresponding standard deviation of error 0.076 and 0.361, respectively. Block importance in the prediction (BIP) for O, N and DRY probe were 1.030, 0.962 and 1.007, respectively. Contour map of variable coefficients showed that hydrogen bonding between the O atom in PO and the NH groups in acetylcholinesterase (AChE) played an important role in the interaction between OP and AChE. Meanwhile, the hydrophobicity of OP also had significant contribution. QSAR based on the MIF descriptors could be a potential means to interpret the mechanisms of ligand-receptor interaction when the receptor was well known.
采用多块偏最小二乘法（MBPLS）方法，基于 O、N 和 DRY 作为探针获得的分子相互作用场（MIF）描述符，构建了 35 种有机磷化合物（OP）与其对家蝇（Musca nebulo L.）24h 急性毒性之间的定量构效关系（QSAR），并用块无标度权重（BUW）技术进行归一化。最佳 QSAR 模型有 8 个主成分，决定系数 R(2)=0.995，留一法交叉验证决定系数 Q(2)=0.865，相应的误差标准差分别为 0.076 和 0.361。O、N 和 DRY 探针的预测重要性（BIP）分别为 1.030、0.962 和 1.007。变量系数轮廓图表明，PO 中的 O 原子与乙酰胆碱酯酶（AChE）中的 NH 基团之间的氢键在 OP 与 AChE 之间的相互作用中起着重要作用。同时，OP 的疏水性也有显著贡献。当受体已知时，基于 MIF 描述符的 QSAR 可能是解释配体-受体相互作用机制的一种潜在手段。
