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ID 48673
file
creator
Ayoub, Ahmed Taha
Elrefaiy, Mohamed Ali
abstract
Lankacidin C, which is an antibiotic produced by the organism Streptomyces rochei, shows considerable antitumor activity. The mechanism of its antitumor activity remained elusive for decades until it was recently shown to overstabilize microtubules by binding at the taxol binding site of tubulin, causing mitotic arrest followed by apoptosis. However, the exact binding mode of lankacidin C inside the tubulin binding pocket remains unknown, an issue that impedes proper structure-based design, modification, and optimization of the drug. Here, we have used computational methods to predict the most likely binding mode of lankacidin C to tubulin. We employed ensemble-based docking in different software packages, supplemented with molecular dynamics simulation and subsequent binding-energy prediction. The molecular dynamics simulations performed on lankacidin C were collectively 1.1 μs long. Also, a multiple-trajectory approach was performed to assess the stability of different potential binding modes. The identified binding mode could serve as an ideal starting point for structural modification and optimization of lankacidin C to enhance its affinity to the tubulin binding site and therefore improve its antitumor activity.
description
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.8b03470.
journal title
ACS Omega
volume
Volume 4
issue
Issue 2
start page
4461
end page
4471
date of issued
2019-02-28
publisher
American Chemical Society
issn
2470-1343
publisher doi
pubmed id
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
publisher
rights
© 2019 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
relation url
department
Graduate School of Advanced Sciences of Matter