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Unraveling the function and structure impact of deleterious missense SNPs in the human OX1R receptor by computational analysis.
Farajzadeh-Dehkordi, Mahvash; Mafakher, Ladan; Harifi, Abbas; Haghdoost-Yazdi, Hashem; Piri, Hossein; Rahmani, Babak.
Afiliación
  • Farajzadeh-Dehkordi M; Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran.
  • Mafakher L; Department of Molecular Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
  • Harifi A; Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
  • Haghdoost-Yazdi H; Department of Electrical and Computer Engineering, University of Hormozgan, Bandar Abbas, Hormozgan, Iran.
  • Piri H; Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran.
  • Rahmani B; Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran.
Sci Rep ; 14(1): 833, 2024 01 08.
Article en En | MEDLINE | ID: mdl-38191899
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Conducta Adictiva / Enfermedades del Sistema Nervioso Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Conducta Adictiva / Enfermedades del Sistema Nervioso Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Reino Unido