Methodology for multi-site ligand-protein docking identification developed for the optimization of spirostenol inhibition of beta-amyloid-induced neurotoxicity.
Chem Biodivers
; 2(11): 1571-9, 2005 Nov.
Article
em En
| MEDLINE
| ID: mdl-17191956
ABSTRACT
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espirostanos
/
Proteínas
/
Modelos Moleculares
/
Peptídeos beta-Amiloides
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
Chem Biodivers
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos