Show simple item record

AuthorS, Udhaya Kumar
AuthorRajan, Bithia
AuthorD, Thirumal Kumar
AuthorR, Hephzibah Cathryn
AuthorV, Samprita Das.
AuthorZayed, Hatem
AuthorWalter, Charles Emmanuel Jebaraj
AuthorRamanathan, Gnanasambandan
AuthorDoss, George Priya
Available date2021-11-22T09:03:41Z
Publication Date2021-11-01
Publication NameJournal of Cellular Biochemistry
Identifierhttp://dx.doi.org/10.1002/jcb.30109
CitationUdhaya Kumar, S, Bithia, R, Thirumal Kumar, D, et al. Comparison of potential inhibitors and targeting fat mass and obesity-associated protein causing diabesity through docking and molecular dynamics strategies. J Cell Biochem. 2021; 122: 1625- 1638. https://doi.org/10.1002/jcb.30109
URIhttp://hdl.handle.net/10576/25060
AbstractGenome-wide association studies (GWAS) have identified an association between polymorphisms in the FTO gene and obesity. The FTO: rs9939609, an intronic variant, is considered a risk allele for developing diabesity in homozygous and heterozygous forms. This study aimed to investigate the molecular structure of the available inhibitors specific to the FTO mutations along with the rs9939609 variant. We identified the best-suited inhibitor molecules for each mutant type containing the rs9939609 risk allele. Missense mutations unique to obesity and containing the risk allele of rs9939609 were retrieved from dbSNP for this study. Further stability testing for the mutations were carried out using DynaMut and iStable tools. Three mutations (G187A, M223V, and I492V) were highly destabilizing the FTO structure. These three mutants and native FTO were docked with each of the nine-inhibitor molecules collected from literature studies with the help of PyRx and AutoDock. Further structural behavior of the mutants and native FTO were identified with molecular dynamics simulations and MM-PBSA analyses, along with the 19complex inhibitor compound. We found the compound 19complex exhibited better binding interactions and is the top candidate inhibitor for the M223V and I492V mutants. This study provided insights into the structural changes caused due to mutations in FTO, and the binding mechanism of the inhibitor molecules. It could aid in developing antiobesity drugs for treating patients with mutations and risk alleles predisposing to obesity.
Languageen
PublisherWiley
SubjectFTO
diabesity
docking
inhibitors
molecular dynamics
obesity
type 2 diabetes mellitus
TitleComparison of potential inhibitors and targeting fat mass and obesity-associated protein causing diabesity through docking and molecular dynamics strategies.
TypeArticle
Pagination1625-1638
Issue Number11
Volume Number122
dc.accessType Abstract Only


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record