Molecular Dynamic Study of Human Prion Protein upon D178N Mutation: New Perspective to H-bonds, Salt Bridges and the Critical Amino Acids

Mansouri, Sakineh; MONAJJEMI, Majıd; Aghaee, Hossein; Zare, Karim; Minuchehr, Zarrin

doi:10.2174/0929866511320070007

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 (ESCI dergilerinde yayınlanan tam makale)
Dergi Adı	Protein and Peptide Letters
Dergi ISSN	0929-8665 Wos Dergi Scopus Dergi
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

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

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

Dergi Adı	PROTEIN AND PEPTIDE LETTERS
Yayıncı	Bentham Science Publishers
Açık Erişim	Hayır
ISSN	0929-8665
E-ISSN	1875-5305
CiteScore	2,4
SJR	0,338
SNIP	0,306

Molecular Dynamic Study of Human Prion Protein upon D178N Mutation: New Perspective to H-bonds, Salt Bridges and the Critical Amino Acids

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