Kurunczi Ludovic, Seclaman Edward, Oprea Tudor I, Crisan Luminita, Simon Zeno
University of Medicine and Pharmacy V. Babes, 2 Eftimie Murgu, 300041 Timisoara, Romania.
J Chem Inf Model. 2005 Sep-Oct;45(5):1275-81. doi: 10.1021/ci050077c.
A homogeneous collection of 45 estrogen agonist derivatives with relative binding affinities measured to the estrogen receptor from Ratus norvegicus was used. The quantitative structure-activity relationships were derived using an improved minimal topologic difference (MTD) method in a partial least-squares (PLS) variant. The spatially assigned analysis of fragment properties can provide receptor site maps, within the limits of the existing series. A steric misfit was found for the steroidal position 2; benefic hydrophobic and van der Waals (enhanced by high polarizability) interactions were found for the 17alpha-CH=CH-X group. MTD-PLS mapping results are confirmed by the experimentally derived estradiol-estrogen receptor binding site contacts (based on X-ray crystallography). Our results suggest that this MTD-PLS method can yield useful results for interactions with receptors of unknown 3D structure and, generally, for the steric rigidity of receptor sites.
使用了一组同质的45种雌激素激动剂衍生物，这些衍生物针对来自褐家鼠的雌激素受体测定了相对结合亲和力。定量构效关系是使用改进的最小拓扑差异（MTD）方法在偏最小二乘法（PLS）变体中得出的。片段性质的空间分配分析可以在现有系列的范围内提供受体位点图谱。在甾体的2位发现了空间不匹配；对于17α-CH=CH-X基团，发现了有益的疏水和范德华（由高极化率增强）相互作用。MTD-PLS图谱结果通过实验得出的雌二醇-雌激素受体结合位点接触（基于X射线晶体学）得到了证实。我们的结果表明，这种MTD-PLS方法对于与未知三维结构的受体相互作用以及一般对于受体位点的空间刚性可以产生有用的结果。
