Publication detail

Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecules based inhibitors against metallothionein-III to study Alzheimer disease

ROY, S. KUMAR, A. BAIG, M. MASAŘÍK, M. PROVAZNÍK, I.

Original Title

Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecules based inhibitors against metallothionein-III to study Alzheimer disease

Type

journal article in Web of Science

Language

English

Original Abstract

Motivation: Metallothionein-III (MT-III) displays neuro-inhibitory activity and is involved in the repair of neuronal damage. An altered expression level of MT-III suggests that it could be a mitigating factor in Alzheimers disease (AD) neuronal dysfunction. Currently there are limited marketed drugs available against MT-III. The inhibitors are mostly pseudo-peptide based with limited ADMET. In our present study, available database InterBioScreen (natural compounds) was screened out for MT-III. Pharmacodynamics and pharmacokinetic studies were performed. Molecular docking and simulations of top hit molecules were performed to study complex stability. Results: Study reveals potent selective molecules that interact and form hydrogen bonds with amino acids Ser-6 and Lys-22 are common to established melatonin inhibitors for MT-III. These include DMHMIO, MCA B and s27533 derivatives. The ADMET profiling was better with comparable interaction energy values. It includes properties like blood brain barrier, hepatotoxicity, druggability, mutagenicity and carcinogenicity. Molecular dynamics studies were performed to validate our findings.

Keywords

Alzheimer disease, Metallothionein-III, Virtual Screening, ADMET, Molecular Dynamics

Authors

ROY, S.; KUMAR, A.; BAIG, M.; MASAŘÍK, M.; PROVAZNÍK, I.

RIV year

2015

Released

1. 4. 2015

Publisher

Elsevier

Location

UK

ISBN

1046-2023

Periodical

METHODS

Year of study

25

Number

4

State

United States of America

Pages from

1

Pages to

26

Pages count

26

BibTex

@article{BUT115027,
  author="Sudeep {Roy} and Akhil {Kumar} and Mohd Hassan {Baig} and Michal {Masařík} and Valentine {Provazník}",
  title="Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecules based inhibitors against metallothionein-III to study Alzheimer disease",
  journal="METHODS",
  year="2015",
  volume="25",
  number="4",
  pages="1--26",
  doi="10.1016/j.ymeth.2015.04.021",
  issn="1046-2023"
}