Methodology for Multi‐Site Ligand–Protein Docking Identification Developed for the Optimization of Spirostenol Inhibition of  β ‐Amyloid‐Induced Neurotoxicity | Zendy

Teper Gary L. | Zendy; Lecanu Laurent | Zendy; Greeson Janet | Zendy; Papadopoulos Vassilios | Zendy

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Methodology for Multi‐Site Ligand–Protein Docking Identification Developed for the Optimization of Spirostenol Inhibition of β ‐Amyloid‐Induced Neurotoxicity

Author(s) -

Teper Gary L.,

Lecanu Laurent,

Greeson Janet,

Papadopoulos Vassilios

Publication year - 2005

Publication title -

chemistry and biodiversity

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.427

H-Index - 70

eISSN - 1612-1880

pISSN - 1612-1872

DOI - 10.1002/cbdv.200590128

Subject(s) - neurotoxicity , docking (animal) , chemistry , binding site , amyloid beta , active site , biochemistry , stereochemistry , computational biology , peptide , enzyme , toxicity , biology , medicine , nursing , organic chemistry

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