Computational exploration of polymorphisms in 5-Hydoxytryptamine 5-HT1A and 5-HT2A receptors associated with psychiatric disease

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 5HT1A 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 5HT2A 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.

► We explored the potential nsSNPs in serotonin (5-HT) receptors.
► 12 classes of serotonin receptors comprising 7743 variants were analyzed.
► Deleterious alleles in 5HT1Aand 5HT2A receptors are reported.