Molecular Dynamic Study of Human Prion Protein upon D178N Mutation: New Perspective to H-bonds, Salt Bridges and the Critical Amino Acids
 
Yazarlar (5)
Sakineh Mansouri Islamic Azad University, Science And Research Branch, İran
Prof. Dr. Majıd MONAJJEMI Islamic Azad University, Science And Research Branch, İran
Hossein Aghaee Islamic Azad University, Science And Research Branch, İran
Karim Zare
Islamic Azad University, Science And Research Branch, İran
Zarrin Minuchehr Islamic Azad University, Science And Research Branch, İran
Makale Türü Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
Dergi Adı Protein and Peptide Letters (Q4)
Dergi ISSN 0929-8665 Dergi Bilgileri (2013)
Makale Dili İngilizce Basım Tarihi 07-2013
Cilt / Sayı / Sayfa 20 / 7 / 775–780 DOI 10.2174/0929866511320070007
Makale Linki http://www.scopus.com/inward/record.url?eid=2-s2.0-84882372820&partnerID=MN8TOARS
UAK Araştırma Alanları
Özet
The molecular dynamics simulation method was used to investigate the structural details for human prion protein (PrPN) and its D178N mutant (PrPM). Root-mean-square fluctuations (RMSFs) and the root-mean-square deviations (RMSDs) showed an increase in the flexibility and high dynamic plasticity of PrPM. Average Total energy for PrP M and PrPN sequentially was-2.975 ×105 (kJmol-1) and-3.193 × 105 (kJmol-1). The results showed conformational rearrangement susceptibility for PrPM. For PrPM, highly surface-exposed Glu196 and Arg136 caused hydrogen bond weakening and electrostatic interactions changes in salt bridges. Hydrogen bond weakening under mutation can be mentioned as the leader of conformational changes and disease-related conversions. Contrary to some reports, the contributions of electrostatic interactions of Glu146-Arg208 and Arg156-Glu196 salt bridges for PrPN is less than of these interactions for PrPM. These interactions can pave the way to conformational changes in PrP M. The results showed that the role of the hydrogen bonds in the stability of human prion protein is more important than these salt bridges. The calculation of the solvent accessible surface area showed that the conformational plasticity in PrPM is mainly due to Asn residues that were solvent exposed. Conformational changes in the specific amino acids can affect metal-ion occupancy and function. The secondary structure has also showed that the structural transition arose from D178N mutation and occurs in specific residues. Our studies support the large scale effects of electrostatic forces at key position 178 of prion. As a result, the conformational rearrangements happen by eliminating only a single negative charge because of the mutation induced global forces in the prion structure. These rearrangements can be considered as a molecular switch, which triggers the initial stages of the conformational transition. © 2013 Bentham Science Publishers.
Anahtar Kelimeler
D178N mutant | Homology modeling | Human prion protein | MD simulations | Salt bridge | Solvent accessible surface area | Stability
BM Sürdürülebilir Kalkınma Amaçları
Atıf Sayıları
Web of Science 4
Scopus 4
Molecular Dynamic Study of Human Prion Protein upon D178N Mutation: New Perspective to H-bonds, Salt Bridges and the Critical Amino Acids

Paylaş

İletişim
  • Kastamonu Üniversitesi Rektörlüğü, Kuzeykent Kampüsü, Merkez/Kastamonu
  • unis@kastamonu.edu.tr 03662801000
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