Molecular docking based virtual screening of natural compounds as potential BACE1 inhibitors: 3D –QSAR pharmacophore mapping and molecular dynamics analysis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216305%3A26220%2F15%3APU114472" target="_blank" >RIV/00216305:26220/15:PU114472 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1080/07391102.2015.1022603" target="_blank" >http://dx.doi.org/10.1080/07391102.2015.1022603</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/07391102.2015.1022603" target="_blank" >10.1080/07391102.2015.1022603</a>

Result language

angličtina

Original language name

Molecular docking based virtual screening of natural compounds as potential BACE1 inhibitors: 3D –QSAR pharmacophore mapping and molecular dynamics analysis

Original language description

Beta-site APP cleaving enzyme1 (BACE1) catalyzes the rate determining step in the generation of A beta peptide and is widely considered as a potential therapeutic drug target for Alzheimers disease (AD). Active site of BACE1 contains catalytic aspartic (Asp) dyad and flap. Asp dyad cleaves the substrate amyloid precursor protein with the help of flap. Currently, there are no marketed drugs available against BACE1 and existing inhibitors are mostly pseudopeptide or synthetic derivatives. There is a need to search for a potent inhibitor with natural scaffold interacting with flap and Asp dyad. This study screens the natural database InterBioScreen, followed by three-dimensional (3D) QSAR pharmacophore modeling, mapping, in silicoADME T predictions to find the potential BACE1 inhibitors. Further, molecular dynamics of selected inhibitors were performed to observe the dynamic structure of protein after ligand binding. All conformations and the residues of binding region were stable but the flap adopted a closed conformation after binding with the ligand. Bond oligosaccharide interacted with the flap as well as catalytic dyad via hydrogen bond throughout the simulation. This led to stabilize the flap in closed conformation and restricted the entry of substrate. Carbohydrates have been earlier used in the treatment of AD because of their low toxicity, high efficiency, good biocompatibility, and easy permeability through the blood–brain barrier. Our finding will be helpful in identify the potential leads to design novel BACE1 inhibitors for AD therapy.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS

ISSN

0739-1102

e-ISSN

1538-0254

Volume of the periodical

9

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

1-11

UT code for WoS article

000368702300002

EID of the result in the Scopus database

2-s2.0-84955674383