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Gly→Ala Point Mutation and Conformation of Poly-Ala Stretch of PABPN1: A Molecular Dynamics Study

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DOI: 10.4236/jbpc.2015.62006    3,881 Downloads   4,380 Views  


Single nucleotide replacing mutations in genes cause a number of diseases, but sometimes these mutations mimic other genetic mutations such as trinucleotide repeats expansions. A mutation in codon GGG→GCG results in Gly→Ala at the N-terminal of PABPN1 protein that mimics the trinucleotide repeat expansion disease called Oculopharyngeal muscular dystrophy (OPMD). Molecular dynamics simulations in water with peptide models having sequence Ac-A10-GA2GG-NHme (peptide A) and Ac-A10A3GG-NHme (peptide B) reveal an increase in the length of helical segment in peptide B. The α-helical length is found to be stable in peptide B with starting geometry of a right handed helix, while in the case peptide A, the helical length is short. The interactions of water molecules at terminals, side chain-backbone interactions and hydrogen bonds provide stability to resultant conformation. The adopted helix by the poly-Ala stretch may lead to masking some other active parts of the PABPN1 that may trigger the aggregation, decrease in degradation and/or impaired function of protein. Hence, further studies with N-terminal may be helpful to understand unclear disease mechanism.

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The authors declare no conflicts of interest.

Cite this paper

Shafique, M. , Garg, M. and Nandel, F. (2015) Gly→Ala Point Mutation and Conformation of Poly-Ala Stretch of PABPN1: A Molecular Dynamics Study. Journal of Biophysical Chemistry, 6, 54-63. doi: 10.4236/jbpc.2015.62006.


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