%0 Journal Article
%T Gly¡úAla Point Mutation and Conformation of Poly-Ala Stretch of PABPN1: A Molecular Dynamics Study
%A Mohd Shafique
%A Mohan Lal Garg
%A Fateh Singh Nandel
%J Journal of Biophysical Chemistry
%P 54-63
%@ 2153-0378
%D 2015
%I Scientific Research Publishing
%R 10.4236/jbpc.2015.62006
%X 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¡úGCG results in Gly¡úAla 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-A<sub>10</sub>-GA<sub>2</sub>GG-NHme (peptide A) and Ac-A<sub>10</sub>A<sub>3</sub>GG-NHme (peptide B) reveal an increase in the length of helical segment in peptide B. The ¦Á-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.
%K Single Nucleotide Polymorphism
%K Gly¡úAla Mutation
%K Poly-Ala
%K OPMD
%K PABPN1
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=56112