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

Abstract

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

Keywords:

• Dopa decarboxylase
• deleterious nsSNP
• structural analysis
• functional analysis
• molecular dynamic simulations

Acknowledgements

The authors would like to express their sincere gratitude to the esteemed Management of Ramaiah Institute of Technology for generously providing the essential computational infrastructure imperative for conducting the research investigations. This study did not obtain any exclusive grants from commercial, public, or non-profit entities.

Disclosure statement

The authors state that they do not have any competing interests.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.