In silico analysis of Single Nucleotide Polymorphisms (SNPs) in human BRAF gene

In silico analysis of Single Nucleotide Polymorphisms (SNPs) in human BRAF gene

BRAF gene mutations are frequently seen in both inherited and somatic diseases. However, the harmful mutations for BRAF gene have not been predicted in silico. Owing to the importance of BRAF gene in cell division, differentiation and secretion processes, the functional analysis was carried out to e...

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Bibliographic Details
Published in:Gene Vol. 508; no. 2; pp. 188 - 196
Main Authors: Hussain, Muhammad Ramzan Manwar, Shaik, Noor Ahmad, Al-Aama, Jumana Yousuf, Asfour, Hani Z., Subhani Khan, Fatima, Masoodi, Tariq Ahmad, Khan, Muhammad Akhtar, Shaik, Nazia Sultana
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 25-10-2012
Subjects:
amino acid composition
amino acids
BRAF gene
cell division
Computational Biology
Disease - genetics
energy
genes
Genomics
Humans
hydrogen bonding
In silico analysis
Models, Molecular
molecular dynamics
Molecular Dynamics Simulation
Mutation - genetics
Pathogenic variants
Phenotype
Polymorphism, Single Nucleotide - genetics
Protein Conformation
protein structure
Proto-Oncogene Proteins B-raf - genetics
screening
secretion
Single Nucleotide Polymorphism
Structure-Activity Relationship
BRAF gene
CFC
A
SIFT
D
E
NLE
F
Genomics
G
In silico analysis
H
I
K
L
N
P
Q
R
S
SNP
T
V
Polyphen
W
Pathogenic variants
Single Nucleotide Polymorphism
OMIM
nsSNP
ANOLEA
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Description
Summary:BRAF gene mutations are frequently seen in both inherited and somatic diseases. However, the harmful mutations for BRAF gene have not been predicted in silico. Owing to the importance of BRAF gene in cell division, differentiation and secretion processes, the functional analysis was carried out to explore the possible association between genetic mutations and phenotypic variations. Genomic analysis of BRAF was initiated with SIFT followed by PolyPhen and SNPs&GO servers to retrieve the 85 deleterious non-synonymous SNPs (nsSNPs) from dbSNP. A total of 5 mutations i.e. c.406T>G (S136A), c.1446G>T (R462I), c.1556 A>G (K499E), c.1860 T>A (V600E) and c.2352 C>T (P764L) that are found to exert benign effects on the BRAF protein structure and function were chosen for further analysis. Protein structural analysis with these amino acid variants was performed by using I-Mutant, FOLD-X, HOPE, NetSurfP, Swiss PDB viewer, Chimera and NOMAD-Ref servers to check their solvent accessibility, molecular dynamics and energy minimization calculations. Our in silico analysis suggested that S136A and P764L variants of BRAF could directly or indirectly destabilize the amino acid interactions and hydrogen bond networks thus explain the functional deviations of protein to some extent. Screening for BRAF, S136A and P764Lvariants may be useful for disease molecular diagnosis and also to design the molecular inhibitors of BRAF pathways. ► Screening of 5nsSNPs by using SIFT, PolyPhen and SNP&GO. ► In silico analysis of BRAF variants. ► Possible exploring of structure-function relationship.
Bibliography:http://dx.doi.org/10.1016/j.gene.2012.07.014
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2012.07.014