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Updated: Aug 15, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
MTD-PLS: a PLS variant of the minimal topologic difference method. III. Mapping interactions between estradiol
Ludovic Kurunczi1, Edward Seclaman, Tudor I Oprea
1University of Medicine and Pharmacy V. Babes, 2 Eftimie Murgu, 300041 Timisoara, Romania. dick@acad-icht.tm.edu.ro
Abstract:
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.
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