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Structure modeling and dynamics driven mutation and phosphorylation analysis of Beta-amyloid peptides.

Singh SK, Singh A, Prakash V, C SK - Bioinformation (2014)

Bottom Line: In our study we have selected three positions: 19ILU, 21ALA and 41ILU in Aβ protein based on their hydrophobic nature and substituted them with PRO ( βSheet breaker).The effects of the substitutions were analysed using molecular dynamics simulation studies.The results validated that the mutations in the specified regions change the hydrophobicity of the protein and the βsheet formation was declined to zero per cent.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Bioinformatics, padmashree Dr.D.Y.Patil University, Belapur-400614, Navi Mumbai, India.

ABSTRACT
The most common characteristics of diverse age-related neurodegenerative diseases are aggregation and accumulation of the misfolded protein in the brain. Alzheimer׳s disease (AD) is one of these protein conformational diseases. Extracellular accumulation of amyloid β (Aβ) is one the neuropathological hallmarks of Alzheimer disease. Various studies have shown that mutation in specific hydrophobic region of Aβ protein inhibit the formation of β sheet, thus aggregation of this protein is stalled. The identification of such mutation in Aβ protein can help us in elucidating the etiology of sporadic Aβ. In our study we have selected three positions: 19ILU, 21ALA and 41ILU in Aβ protein based on their hydrophobic nature and substituted them with PRO ( βSheet breaker). The effects of the substitutions were analysed using molecular dynamics simulation studies. The results validated that the mutations in the specified regions change the hydrophobicity of the protein and the βsheet formation was declined to zero per cent.

No MeSH data available.


Related in: MedlinePlus

Residues 19, 21, and 41 are replaced by PROLINE tostudy the effect of mutants (Arguslab 4.0..1) and Comparing thehydrophobicity of the wildtype and mutants in UCSF ChimereVers;ion. 1.6.2 revelated that hydrophobicity of self-recognitionsite of the peptide was reduced with might reduce theiraggregative ability.
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Figure 6: Residues 19, 21, and 41 are replaced by PROLINE tostudy the effect of mutants (Arguslab 4.0..1) and Comparing thehydrophobicity of the wildtype and mutants in UCSF ChimereVers;ion. 1.6.2 revelated that hydrophobicity of self-recognitionsite of the peptide was reduced with might reduce theiraggregative ability.

Mentions: Beta sheet is responsible for the formation of aggregates of BetaAmyloid (Aβ) in the Brain cells and since Proline (P) is a Betasheet breaker, so Proline was used in order to reduce the Betasheet formation and thus to reduce its aggregation too (Figure 6). Simulation of Wild type Beta amyloid at 25 nano second byusing Gromacs shows that Beta sheet is formed at the rate of9.5% while for mutant Beta Amyloid i.e. F19P, F21P and I41P,Beta sheet formation was decreased to Zero (Figure 7 & Figure 8).Thus mutation (substitution of Proline) at position 19, 21 and 41show the Beta sheet formation thus resulting to noaggregation of Beta Amyloid and thus can be employed for thetreatment of Alzheimer disease.


Structure modeling and dynamics driven mutation and phosphorylation analysis of Beta-amyloid peptides.

Singh SK, Singh A, Prakash V, C SK - Bioinformation (2014)

Residues 19, 21, and 41 are replaced by PROLINE tostudy the effect of mutants (Arguslab 4.0..1) and Comparing thehydrophobicity of the wildtype and mutants in UCSF ChimereVers;ion. 1.6.2 revelated that hydrophobicity of self-recognitionsite of the peptide was reduced with might reduce theiraggregative ability.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4209365&req=5

Figure 6: Residues 19, 21, and 41 are replaced by PROLINE tostudy the effect of mutants (Arguslab 4.0..1) and Comparing thehydrophobicity of the wildtype and mutants in UCSF ChimereVers;ion. 1.6.2 revelated that hydrophobicity of self-recognitionsite of the peptide was reduced with might reduce theiraggregative ability.
Mentions: Beta sheet is responsible for the formation of aggregates of BetaAmyloid (Aβ) in the Brain cells and since Proline (P) is a Betasheet breaker, so Proline was used in order to reduce the Betasheet formation and thus to reduce its aggregation too (Figure 6). Simulation of Wild type Beta amyloid at 25 nano second byusing Gromacs shows that Beta sheet is formed at the rate of9.5% while for mutant Beta Amyloid i.e. F19P, F21P and I41P,Beta sheet formation was decreased to Zero (Figure 7 & Figure 8).Thus mutation (substitution of Proline) at position 19, 21 and 41show the Beta sheet formation thus resulting to noaggregation of Beta Amyloid and thus can be employed for thetreatment of Alzheimer disease.

Bottom Line: In our study we have selected three positions: 19ILU, 21ALA and 41ILU in Aβ protein based on their hydrophobic nature and substituted them with PRO ( βSheet breaker).The effects of the substitutions were analysed using molecular dynamics simulation studies.The results validated that the mutations in the specified regions change the hydrophobicity of the protein and the βsheet formation was declined to zero per cent.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Bioinformatics, padmashree Dr.D.Y.Patil University, Belapur-400614, Navi Mumbai, India.

ABSTRACT
The most common characteristics of diverse age-related neurodegenerative diseases are aggregation and accumulation of the misfolded protein in the brain. Alzheimer׳s disease (AD) is one of these protein conformational diseases. Extracellular accumulation of amyloid β (Aβ) is one the neuropathological hallmarks of Alzheimer disease. Various studies have shown that mutation in specific hydrophobic region of Aβ protein inhibit the formation of β sheet, thus aggregation of this protein is stalled. The identification of such mutation in Aβ protein can help us in elucidating the etiology of sporadic Aβ. In our study we have selected three positions: 19ILU, 21ALA and 41ILU in Aβ protein based on their hydrophobic nature and substituted them with PRO ( βSheet breaker). The effects of the substitutions were analysed using molecular dynamics simulation studies. The results validated that the mutations in the specified regions change the hydrophobicity of the protein and the βsheet formation was declined to zero per cent.

No MeSH data available.


Related in: MedlinePlus