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A Computationally-Based Hazard Identification Algorithm That Incorporates Ligand Flexibility. 1. Identification Of Potential Androgen Receptor Ligands, Steven P. Bradbury, Ovanes Mekenyan, Julian Ivanov, Stoyan Karabunarliev, Gerald T. Ankley, Walter Karcher

Steven P. Bradbury

To advance techniques for screening large data sets of diverse structures for toxicologically active compounds, an algorithm was developed that is not dependent upon a predetermined and specified toxicophore or an alignment of conformers to a lead compound. Instead, the approach provides the means to identify and quantify specific global and local stereoelectronic characteristics associated with active compounds through a comparison of energeticallyreasonable conformer distributions for specific descriptors. To illustrate the algorithm, the stereoelectronic requirements associated with the binding affinity of 28 steroidal and non-steroidal ligands to the androgen receptor were defined. Common ranges of interatomic distances, atomic charges, and …