Introduction: Risperidone is atypical antipsychotic medication commonly used to control behavioral symptoms in children with autism and widely considered a first-line treatment for acute and maintenance treatment of schizophrenia and bipolar mania. However, the response to risperidone is varied between patients due to genetic factors such as dopamine receptor genes. Methods: Using state-of-the-art tools, the current study designed to predict the most deleterious SNPs of the five ( DRD1, DRD2, DRD3, DRD4 and DRD5 ) dopamine receptors genes, and their impact on the function and structure of dopamine receptor protein and the binding with risperidone. In-silico tools such as SIFT, PolyPhen2, PANTHER, PROVEAN, SNPs & GO, CRAVAT-VEST score, Mutation Assessor, FannsDB-CONDEL score, predict SNP and SNAP2 were subjected to predicting the deleterious nature of 1581 non-synonymous SNPs (nsSNP) of dopamine receptors genes. Results: The analysis predicted the most deleterious nsSNPs in each dopamine receptor: rs759268810 in DRD1 , rs866976053 in DRD2 , rs1274871399 in DRD3 , rs745604469 in DRD4 , and rs778635010 in DRD5 . Significant reduction in the binding free energy in the mutant (F198C: S score = − 7.29 kcal/mol) in the D2 subtype of the dopamine receptor compared to the wild (F198: S score = − 8.73 kcal/mol) at the interaction analysis with risperidone. Cumulative analysis of the interaction between risperidone and dopamine receptor protein revealed the rs866976053 as the most deleterious nsSNP among the 1581 nsSNPs of the dopamine receptor genes. Conclusion: The observation of the state-of-the-art tools-based analysis and observations of MD simulations prioritized the F198C of DRD2 as a candidate variant for wet lab studies to find its impact on drug efficacy for managing autism, schizophrenia and bipolar mania. Keywords: autism, risperidone, schizophrenia, bipolar mania, dopamine receptor, mutation, DRD2, docking
Almandil et al. (Wed,) studied this question.