Show simple item record

dc.contributor.authorAlam, Md Shahed
dc.contributor.authorSaleh, Md Abu
dc.contributor.authorMozibullah, Md
dc.contributor.authorRiham, Ashik Tanvir
dc.contributor.authorSolayman, Md
dc.contributor.authorGan, Siew Hua
dc.date.accessioned2021-11-25T01:08:19Z
dc.date.available2021-11-25T01:08:19Z
dc.date.issued2021
dc.identifier.issn1476-9271
dc.identifier.doi10.1016/j.compbiolchem.2021.107587
dc.identifier.urihttp://hdl.handle.net/10072/410069
dc.description.abstractHuman dihydrofolate reductase (DHFR) is a conserved enzyme that is central to folate metabolism and is widely targeted in pathogenic diseases as well as cancers. Although studies have reported the fact that genetic mutations in DHFR leads to a rare autosomal recessive inborn error of folate metabolism and drug resistance, there is a lack of an extensive study on how the deleterious non-synonymous SNPs (nsSNPs) disrupt its phenotypic effects. In this study, we aim at discovering the structural and functional consequences of nsSNPs in DHFR by employing a combined computational approach consisting of ten recently developed in silico tools for identification of damaging nsSNPs and molecular dynamics (MD) simulation for getting deeper insights into the magnitudes of damaging effects. Our study revealed the presence of 12 most deleterious nsSNPs affecting the native phenotypic effects, with three (R71T, G118D, Y122D) identified in the co-factor and ligand binding active sites. MD simulations also suggested that these three SNPs particularly Y122D, alter the overall structural flexibility and dynamics of the native DHFR protein which can provide more understandings into the crucial roles of these mutants in influencing the loss of DHFR function.
dc.description.peerreviewedYes
dc.languageeng
dc.publisherElsevier BV
dc.relation.ispartofpagefrom107587
dc.relation.ispartofjournalComputational Biology and Chemistry
dc.relation.ispartofvolume95
dc.subject.fieldofresearchBioinformatics and computational biology
dc.subject.fieldofresearchInformation and computing sciences
dc.subject.fieldofresearchcode3102
dc.subject.fieldofresearchcode46
dc.subject.keywordsDHFR
dc.subject.keywordsIn silico
dc.subject.keywordscancer
dc.subject.keywordsfolate
dc.subject.keywordsmolecular dynamics simulations
dc.titleComputational algorithmic and molecular dynamics study of functional and structural impacts of non-synonymous single nucleotide polymorphisms in human DHFR gene.
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationAlam, MS; Saleh, MA; Mozibullah, M; Riham, AT; Solayman, M; Gan, SH, Computational algorithmic and molecular dynamics study of functional and structural impacts of non-synonymous single nucleotide polymorphisms in human DHFR gene, Computational Biology and Chemistry, 2021, 95, pp. 107587
dcterms.dateAccepted2021-10-01
dcterms.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated2021-11-11T04:47:23Z
dc.description.versionAccepted Manuscript (AM)
gro.rights.copyright© 2021 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorSolayman, Md.


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record