PMID- 27999707
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2090-9918 (Print)
IS  - 2090-7818 (Electronic)
IS  - 2090-9918 (Linking)
VI  - 2016
DP  - 2016
TI  - Novel Concepts for Drug Hypersensitivity Based on the Use of Long-Time Scale 
      Molecular Dynamic Simulation.
PG  - 9520361
LID - 10.1155/2016/9520361 [doi]
LID - 9520361
AB  - The discovery that several drug hypersensitivity reactions (DHRs) are associated 
      with specific human leukocyte antigen (HLA) alleles has attracted increasing 
      research interest. However, the underlying mechanisms of these HLA-induced DHRs 
      remain unclear, especially for drug-induced immediate activation of T-cell clones 
      (TCCs). Recently, a novel hypothesis involving partial detachment between 
      self-peptide(s) and the HLA molecule (altered peptide-HLA (pHLA) model) has been 
      proposed to explain these phenomena. In order to clarify this hypothesis, we 
      performed long-timescale molecular dynamics (MD) simulations. We focused on 
      HLA-B⁎57:01-restricted abacavir hypersensitivity reactions (AHRs), one of the 
      most famous DHRs. One of the simulation results showed that this altered-pHLA 
      model might be driven by an increase in the distance not only between HLA and 
      self-peptides but also between the alpha(1) and alpha(2) helices of HLA. Our findings 
      provide novel insights into abacavir-induced immediate activation of TCCs and 
      these findings might also be applied to other DHRs, such as 
      HLA-B⁎58:01-restricted allopurinol hypersensitivity reactions.
FAU - Murai, Takahiro
AU  - Murai T
AD  - Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, 
      Suita, Osaka 565-0871, Japan.
FAU - Kawashita, Norihito
AU  - Kawashita N
AD  - Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, 
      Suita, Osaka 565-0871, Japan; Research Institute for Microbial Diseases, Osaka 
      University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
FAU - Tian, Yu-Shi
AU  - Tian YS
AUID- ORCID: 0000-0002-8988-9453
AD  - Graduate School of Information Science and Technology, Osaka University, 1-5 
      Yamadaoka, Suita, Osaka 565-0871, Japan.
FAU - Takagi, Tatsuya
AU  - Takagi T
AUID- ORCID: 0000-0002-0044-0722
AD  - Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, 
      Suita, Osaka 565-0871, Japan; Research Institute for Microbial Diseases, Osaka 
      University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
LA  - eng
PT  - Journal Article
DEP - 20161123
PL  - Egypt
TA  - J Pharm (Cairo)
JT  - Journal of pharmaceutics
JID - 101655539
PMC - PMC5141551
COIS- The authors declare that there is no conflict of interests regarding the 
      publication of this paper.
EDAT- 2016/12/22 06:00
MHDA- 2016/12/22 06:01
PMCR- 2016/11/23
CRDT- 2016/12/22 06:00
PHST- 2016/07/04 00:00 [received]
PHST- 2016/11/03 00:00 [accepted]
PHST- 2016/12/22 06:00 [entrez]
PHST- 2016/12/22 06:00 [pubmed]
PHST- 2016/12/22 06:01 [medline]
PHST- 2016/11/23 00:00 [pmc-release]
AID - 10.1155/2016/9520361 [doi]
PST - ppublish
SO  - J Pharm (Cairo). 2016;2016:9520361. doi: 10.1155/2016/9520361. Epub 2016 Nov 23.