title: Computational exploration of polymorphisms in 5-hydoxytryptamine 5-HT₁A and 5-HT₂A receptors associated with psychiatric disease.
abstract: The huge polymorphic data have been prioritized towards a specific disease based on sequence and structure homology tools to a large extent. In this study, we have explored the potential non-synonymous Single Nucleotide Polymorphism (nsSNP) in serotonin (5-HT) receptors involved in psychotic syndromes and their response pathway. The most damaging point mutations were screened from 12 classes of serotonin receptors comprising 7743 variants. In 5HT(1A) receptor, two alleles were found to be highly deleterious located at ligand binding extracellular-2 and one at intracellular loop-3 domains. Similarly, we found two alleles predicted to be highly damaging in 5HT(2A) residing at N and C-Terminal domains. The above alleles were further confirmed based on their flexibility and stability difference using the molecular dynamic simulation analysis. Integrating these results appeared promising for being able to filter out potential non-synonymous Single Nucleotide Polymorphisms for neuropsychiatric disorders.
authors.affiliation: Bioinformatics Division, School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu 632014, India.
authors.forename: J Febin Prabhu
authors.initials: JF
authors.lastname: Dass
authors.forename: C
authors.initials: C
authors.lastname: Sudandiradoss
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D003198:Computer Simulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D001523:Mental Disorders / Q000235:genetics*; D008957:Models, Genetic; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry / Q000235:genetics*; D044402:Receptor, Serotonin, 5-HT2A / Q000737:chemistry / Q000235:genetics*; D012307:Risk Factors; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D020506:Untranslated Regions
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D020506:Untranslated Regions; D044282:Receptor, Serotonin, 5-HT1A