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AuthorThirumal Kumar, D
AuthorSusmita, B
AuthorJudith, E
AuthorPriyadharshini Christy, J
AuthorGeorge Priya Doss, C
AuthorZayed, Hatem
Available date2019-03-05T10:36:30Z
Publication Date2019-02-26
Publication NameAdvances in Protein Chemistry and Structural Biologyen_US
Identifierhttp://dx.doi.org/10.1016/bs.apcsb.2018.11.005
CitationThirumal Kumar D, Susmita B, Judith E, Priyadharshini Christy J, George Priya Doss C, Zayed H. Elucidating the role of interacting residues of the MSH2-MSH6 complex in DNA repair mechanism: A computational approach. Adv Protein Chem Struct Biol. 2019;115:325-350. doi: 10.1016/bs.apcsb.2018.11.005.
ISSN1876-1623
URIhttp://hdl.handle.net/10576/11371
AbstractThe DNA repair system is crucial to repair the error resulting in DNA replication. MSH2-MSH6 protein complex plays a significant role in maintaining the mismatch repair mechanism. Mutations in the interface between the two proteins compromise their function in the repair process. The present study aims to understand the impact of missense mutations in the interacting sites of the MSH2-MSH6 protein complex. MSH6 is unstable due to the disordered N-terminal domain. This is stabilized by the MSH2 hetero-dimerization. We used pathogenicity and stability predictors to identify the missense mutations that could be more pathogenic with the destabilizing property. The mutations W764C of MSH2, and L1201F and G1316E of MSH6 were predicted to be highly deleterious and destabilizing by all the in silico predictors. The dynamic motion of the native and mutant (W764C) MSH2-MSH6 protein complexes was further investigated using Molecular Dynamics Simulations of the GROMACS package. The Root Mean Square Deviation (RMSD), Radius of Gyration (Rg), and change in a number of intramolecular hydrogen bonds (H-bonds) were analyzed using the embedded packages of GROMACS. From the simulation studies, we observed higher deviation, lower protein compactness, and a decrease in the number of intramolecular hydrogen bonds in the mutant W764C MSH2-MSH6 protein complex. The observed results from the computational methods suggest the involvement of higher structural impact on the MSH2-MSH6 protein complex upon W764C mutation could affect the DNA repair mechanism.
Languageen
PublisherElsevier
SubjectDNA repair mechanism
SubjectMSH2-MSH6
SubjectMolecular dynamics
SubjectW764C
TitleElucidating the role of interacting residues of the MSH2-MSH6 complex in DNA repair mechanism: A computational approach.
TypeArticle
Pagination325-350
Volume Number115
ESSN1876-1631


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