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

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 <i>in silico</i> 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 <i>in silico</i> 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.

多巴脱羧酶（Dopa Decarboxylase, DDC）基因在多巴胺（dopamine）、血清素（serotonin）及组胺（histamine）等生物胺（biogenic amines）的合成过程中发挥关键作用。该基因的非同义单核苷酸多态性（Non-synonymous single nucleotide polymorphisms, nsSNPs）已被证实与多种神经退行性疾病密切相关。本研究针对DDC基因的nsSNPs开展了全面的计算机模拟（in silico）分析，以评估其潜在的功能效应及与疾病转归的关联。
研究团队通过公开数据库获取了DDC基因所有nsSNPs的完整列表，并利用29种计算工具与算法，对这些nsSNPs在蛋白质结构、功能及稳定性层面的影响进行了系统表征。此外，本研究还实施了基于人群的关联研究，以探究特定nsSNPs与关节炎的潜在关联。
本研究共鉴定出4个全新的DDC基因nsSNPs，它们对蛋白质的结构与功能具有显著影响。通过分子动力学模拟（Molecular Dynamics Simulations, MDS），研究人员观察到特定nsSNPs可诱导DDC蛋白质稳定性发生改变。进一步的基于人群的关联研究显示，部分DDC基因nsSNPs与帕金森病（Parkinson’s disease）、痴呆（dementia）等多种神经系统疾病存在潜在关联。
本研究采用的计算机模拟（in silico）分析方法，为DDC基因nsSNPs的功能效应提供了极具价值的洞察。上述发现为阐明认知障碍的细胞机制提供了新的视角。此外，鉴定与疾病相关的DDC基因nsSNPs，有望推动个性化靶向治疗策略的开发。