کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2773015 1567893 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Screening of mutations affecting protein stability and dynamics of FGFR1—A simulation analysis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی بالینی
پیش نمایش صفحه اول مقاله
Screening of mutations affecting protein stability and dynamics of FGFR1—A simulation analysis
چکیده انگلیسی

Single amino acid substitutions in Fibroblast Growth Factor Receptor 1 (FGFR1) destabilize protein and have been implicated in several genetic disorders like various forms of cancer, Kallamann syndrome, Pfeiffer syndrome, Jackson Weiss syndrome, etc. In order to gain functional insight into mutation caused by amino acid substitution to protein function and expression, special emphasis was laid on molecular dynamics simulation techniques in combination with in silico tools such as SIFT, PolyPhen 2.0, I-Mutant 3.0 and SNAP. It has been estimated that 68% nsSNPs were predicted to be deleterious by I-Mutant, slightly higher than SIFT (37%), PolyPhen 2.0 (61%) and SNAP (58%). From the observed results, P722S mutation was found to be most deleterious by comparing results of all in silico tools. By molecular dynamics approach, we have shown that P722S mutation leads to increase in flexibility, and deviated more from the native structure which was supported by the decrease in the number of hydrogen bonds. In addition, biophysical analysis revealed a clear insight of stability loss due to P722S mutation in FGFR1 protein. Majority of mutations predicted by these in silico tools were in good concordance with the experimental results.


► Predicting the significance of novel genetic variants associated with FGFR1 gene using in silico tools.
► Biophysical validation of nsSNPs in FGFR1 gene.
► Analysis of structural and functional impact due to mutation by molecular dynamics approach.
► Stability loss of P722S mutation was observed in RMSD, RMSF and Hydrogen bond analysis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Applied & Translational Genomics - Volume 1, 1 December 2012, Pages 37–43
نویسندگان
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