PMID- 38191899
OWN - NLM
STAT- MEDLINE
DCOM- 20240110
LR  - 20240111
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 14
IP  - 1
DP  - 2024 Jan 8
TI  - Unraveling the function and structure impact of deleterious missense SNPs in the 
      human OX1R receptor by computational analysis.
PG  - 833
LID - 10.1038/s41598-023-49809-4 [doi]
LID - 833
AB  - The orexin/hypocretin receptor type 1 (OX1R) plays a crucial role in regulating 
      various physiological functions, especially feeding behavior, addiction, and 
      reward. Genetic variations in the OX1R have been associated with several 
      neurological disorders. In this study, we utilized a combination of sequence and 
      structure-based computational tools to identify the most deleterious missense 
      single nucleotide polymorphisms (SNPs) in the OX1R gene. Our findings revealed 
      four highly conserved and structurally destabilizing missense SNPs, namely R144C, 
      I148N, S172W, and A297D, located in the GTP-binding domain. Molecular dynamics 
      simulations analysis demonstrated that all four most detrimental mutant proteins 
      altered the overall structural flexibility and dynamics of OX1R protein, 
      resulting in significant changes in the structural organization and motion of the 
      protein. These findings provide valuable insights into the impact of missense 
      SNPs on OX1R function loss and their potential contribution to the development of 
      neurological disorders, thereby guiding future research in this field.
CI  - (c) 2024. The Author(s).
FAU - Farajzadeh-Dehkordi, Mahvash
AU  - Farajzadeh-Dehkordi M
AD  - Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran.
AD  - Department of Molecular Medicine, Qazvin University of Medical Sciences, Qazvin, 
      Iran.
FAU - Mafakher, Ladan
AU  - Mafakher L
AD  - Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz 
      Jundishapur University of Medical Sciences, Ahvaz, Iran.
FAU - Harifi, Abbas
AU  - Harifi A
AD  - Department of Electrical and Computer Engineering, University of Hormozgan, 
      Bandar Abbas, Hormozgan, Iran.
FAU - Haghdoost-Yazdi, Hashem
AU  - Haghdoost-Yazdi H
AD  - Cellular and Molecular Research Center, Research Institute for Prevention of 
      Non-Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran.
FAU - Piri, Hossein
AU  - Piri H
AD  - Cellular and Molecular Research Center, Research Institute for Prevention of 
      Non-Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran.
FAU - Rahmani, Babak
AU  - Rahmani B
AD  - Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran. 
      b.rahmanigene@gmail.com.
AD  - Department of Molecular Medicine, Qazvin University of Medical Sciences, Qazvin, 
      Iran. b.rahmanigene@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20240108
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Orexin Receptors)
SB  - IM
MH  - Humans
MH  - Polymorphism, Single Nucleotide
MH  - *Behavior, Addictive
MH  - Molecular Dynamics Simulation
MH  - Morphogenesis
MH  - Orexin Receptors
MH  - *Nervous System Diseases
PMC - PMC10774445
COIS- The authors declare no competing interests.
EDAT- 2024/01/09 06:42
MHDA- 2024/01/10 06:42
PMCR- 2024/01/08
CRDT- 2024/01/09 00:05
PHST- 2023/08/24 00:00 [received]
PHST- 2023/12/12 00:00 [accepted]
PHST- 2024/01/10 06:42 [medline]
PHST- 2024/01/09 06:42 [pubmed]
PHST- 2024/01/09 00:05 [entrez]
PHST- 2024/01/08 00:00 [pmc-release]
AID - 10.1038/s41598-023-49809-4 [pii]
AID - 49809 [pii]
AID - 10.1038/s41598-023-49809-4 [doi]
PST - epublish
SO  - Sci Rep. 2024 Jan 8;14(1):833. doi: 10.1038/s41598-023-49809-4.