A Systematic Approach To Investigate The Predicted Effect Of Nonsynonymous SNPs In The Human Prion Protein Gene: A Molecular Modeling And Molecular Dynamics Study | 9338
Journal of Computer Science & Systems Biology
Like us on:
Our Group organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.
Human prion diseases are caused by misfolding or aggregation of the Human Prion Protein (HuPrP). Missense mutations in
the HuPrP gene, contribute to conversion of HuPr
and amyloid formation. In order to better understand and
predict the role of HuPrP mutations, we developed the following procedure: first, the Human Genome Variation database and
dbSNP databases were consulted, and literature were reviewed for the retrieval of aggregation-related nsSNPs of the HuPrP gene.
Next, we used three different methods-Polymorphism Phenotyping (PolyPhen), PANTHER, and Auto-Mute-to predict the effect
of nsSNPs on the phenotype. The predictions against experimentally reported effects of these nsSNPs were compared to evaluate
the accuracy of the three methods. Also, structural analyses of the native protein against mutated models were investigated using
molecular modeling and molecular dynamics (MD) simulation methods. From these results, three missense mutations, from
different functional groups, including V210I, Q212P, and E219K were selected and extensive molecular dynamics simulations
of these three mutations performed to compare their dynamics and conformations to those of the wild type HuPrP in both
monomeric and dimeric forms. In conclusion, our results show the applicability of our procedure for the prediction of damaging
nsSNPs. Our study also elucidates the obvious relationship between predicted values of aggregation-related nsSNPs in HuPrP
gene and molecular modeling and MD simulations results.
Jahandideh received his Ph.D. in Biophysics from Tarbiat Modares University, Tehran, Iran in 2010. He then took his postdoctoral training in
computational biology at the University of Alabama at Birmingham and Sanford-Burnham Medical Research Institute, La Jolla, California. Before
moving to USA, he has worked as an Assistant Professor and Vice-Chancellor for Research in the Department of Medical Physics at Shiraz
University of Medical Sciences, Shiraz, Iran. He has published more than 25 papers in reputed journals and reviews research manuscripts at number
of journals, including Bioinformatics, BMC Bioinformatics, and BMC Genomics.
Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals