Methodology for Multi-Site Ligand-Protein Docking Identification Developed for the Optimization of Spirostenol Inhibition of [beta]-Amyloid-Induced Neurotoxicity

Spirostenol steroids have been found to inhibit [beta]-amyloid-induced neurotoxicity. We have evaluated in parallel experimental and molecular-modeling studies the relative effectiveness of 17 (22R)-hydroxycholesterol derivatives in binding to the target peptide. Our results support the previous evi...

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Published inChemistry & biodiversity Vol. 2; no. 11; pp. 1571 - 1579
Main Authors Teper, Gary L, Lecanu, Laurent, Greeson, Janet, Papadopoulos, Vassilios
Format Journal Article
LanguageEnglish
Published 01.11.2005
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Summary:Spirostenol steroids have been found to inhibit [beta]-amyloid-induced neurotoxicity. We have evaluated in parallel experimental and molecular-modeling studies the relative effectiveness of 17 (22R)-hydroxycholesterol derivatives in binding to the target peptide. Our results support the previous evidence that [beta]-amyloid offers multiple docking sites for these steroids. Molecular modeling allowed for the correlation of spirostenol candidate structural differences with a choice of proposed active sites. A multi-site identification technique based on a Site-Identifier Matrix (SIM) was developed that clearly showed the uniqueness of our lead (maximum neurotoxicity inhibition) candidate SP233, with a nearly equal docking affinity for two sites.
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ISSN:1612-1872
1612-1880
DOI:10.1002/cbdv.200590128