肺腺癌（LUAD）是肺癌中最突出的组织学亚型，是癌症死亡率的主要原因。高突变率和糖酵解率是肺癌中报道的主要改变。在我们的研究中，我们阐明了关键糖酵解酶 3-磷酸甘油醛脱氢酶 (GAPDH) 和相关 SNP 在 LUAD 进展中的结构和功能作用。我们的基因表达分析揭示了 LUAD 中 GAPDH 的高表达。计算机工具和分析用于有害 SNP 的识别和表征。分子对接和动力学模拟 (MDS) 研究表征了优先有害突变的结构后果。基于序列的分析识别 GAPDH 中的 SNP，结果发现 28 个有害 SNP，其中 6 个 SNP 显示出有害和破坏作用。基于结构的分析产生了保守域中 rs ids rs11549328 (D39Y) 和 rs200102749 (S51Y) 的 2 个稳定 SNP。 GAPDH 序列的 IDR 和 PTM 分析得出了 191 至 194 个位置的 IDR 区域，经过 PTM 修饰后，IDR 得分为 0.511、0.520、0.517 和 0.503。已鉴定的有害 SNP（D39Y 和 S51Y）属于功能性和保守性。 GAPDH 的结构域。此外，GAPDH 的 IDR 区域内 PTM 的存在可能有助于增强 LUAD 中的糖酵解活性。我们的研究结果为 LUAD 进展中 GAPDH 的病理学方面提供了潜在的背景有害突变体。版权所有 © 2024。由 Elsevier Inc. 出版。

Lung adenocarcinoma (LUAD) is the most prominent histological subtype among the lung cancer which is a leading cause in the cancer mortality rate. High mutational and glycolytic rates are the major reported alterations in the lung cancer. Here in our study we are elucidating the structural and functional role of key glycolytic enzyme Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and associated SNPs in LUAD progression.Our gene expression analysis reveals high expression of GAPDH in the LUAD. In silico tools and analysis were used for the identification and characterization of the deleterious SNPs. Molecular Docking and dynamics simulations (MDS) studies characterized the structural consequences of prioritized deleterious mutations.The sequence based analysis to identify SNPs in GAPDH resulted in 28 deleterious SNPs and 6 SNPs among them showed deleterious and damaging effect. The structural based analysis resulted in 2 stabilizing SNPs of rs ids rs11549328 (D39Y) and rs200102749 (S51Y) in the conserved domain. The IDR and PTM analysis of the GAPDH sequence resulted an IDR region from 191 to 194 positions with an IDR score of 0.511, 0.520, 0.517 and 0.503 with the PTM modifications.The identified deleterious SNPs (D39Y and S51Y) fall in the functional and conserved domain of GAPDH. In addition, the existence of PTMs within the IDR region of the GAPDH may contribute to its enhanced glycolytic activity in LUAD. The results of our study provide potential background deleterious mutants the pathological aspect of GAPDH in LUAD progression.Copyright © 2024. Published by Elsevier Inc.