A computational study on structural and functional consequences of nsSNPs in human dopa decarboxylase

S. Birendra Kumar, Aishwarya Girish, Samruddhi Sutar, Suheeth Amberi Premanand, Vrinda Garg, Arvind Kumar Yadav,Rohit Shukla,T. P. Krishna Murthy,Tiratha Raj Singh

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS(2024)

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摘要
The Dopa Decarboxylase (DDC) gene plays an important role in the synthesis of biogenic amines such as dopamine, serotonin, and histamine. Non-synonymous single nucleotide polymorphisms (nsSNPs) in the DDC gene have been linked with various neurodegenerative disorders. In this study, a comprehensive in silico analysis of nsSNPs in the DDC gene was conducted to assess their potential functional consequences and associations with disease outcomes. Using publicly available databases, a complete list of nsSNPs in the DDC gene was obtained. 29 computational tools and algorithms were used to characterise the effects of these nsSNPs on protein structure, function, and stability. In addition, the population-based association studies were performed to investigate possible associations between specific nsSNPs and arthritis. Our research identified four novel DDC gene nsSNPs that have a major impact on the structure and function of proteins. Through molecular dynamics simulations (MDS), we observed changes in the stability of the DDC protein induced by specific nsSNPs. Furthermore, population-based association studies have revealed potential associations between certain DDC nsSNPs and various neurological disorders, including Parkinson's disease and dementia. The in silico approach used in this study offers insightful information about the functional effects of nsSNPs in the DDC gene. These discoveries provide insight into the cellular processes that underlie cognitive disorders. Furthermore, the detection of disease-associated nsSNPs in the DDC gene may facilitate the development of tailored and targeted therapy approaches.Communicated by Ramaswamy H. Sarma
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关键词
Dopa decarboxylase,deleterious nsSNP,structural analysis,functional analysis,molecular dynamic simulations
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