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J Mol Model ; 28(3): 60, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35156141

RESUMO

For the purpose of discovering potential inhibitors of ß-amyloid (BACE1), which is a crucial element in Alzheimer's disease (AD) pathogenesis, an in silico study of naturally occurring compounds was performed using precise computational approaches. Autodock4 package was preliminary used to predict the binding affinities to BACE1 of more than four thousand compounds presented in the Vietnamese plants (VIETHERB) database. Based on docking results, twenty top-lead compounds having the largest docking energy to BACE1 were rigorously examined using steered molecular dynamics (SMD) simulations. Interestingly, SMD results found that the binding affinity values of three compounds, including myricetin 3-O-(3''-galloylrhamnopyranoside), quercetin 3-O-neohesperidoside, and hydroxysafflor yellow A, are remarkably higher than that of the well-known BACE1 inhibitor, 23I, and these compounds can thus be considered the promising candidates for inhibitors of BACE1.


Assuntos
Doença de Alzheimer , Secretases da Proteína Precursora do Amiloide , Inibidores Enzimáticos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Ácido Aspártico Endopeptidases/metabolismo , Bases de Dados Factuais , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular
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