Lysosomal storage diseases comprise different forms of autosomal recessive disorders from which GM1 gangliosidosis has categorized by the accumulation of complex glycolipids associated with a range of progressive neurologic phenotypes. GM1 gangliosidosis is an inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. GM1 has three main types of onsets, namely infantile (type I), juvenile (type II), and adult (type III) forms. This study provides a series of computational methods that examine the mutations that occurred in GLB1 protein. Initially, the mutational analysis started with 689 amino acid variants for a sequence-based screening and it was done with quite a few In-silico tools to narrow down the most significant variants by utilizing the standard tools; namely, Evolutionary analysis (77 variants), Pathogenicity prediction (44 variants), Stability predictions (30 variants), Biophysical functions (19 variants) and according to the binding site of protein structure with PDB ID 3THC, seven variants (Y83D, Y83H, Y270S, Y270D, W273R, W273D, and Y333H) were narrowed down. Structure based analysis was performed to understand the interacting profile of the native protein and variants with Miglustat; which is the currently used FDA drug as an alternative to enzyme replacement therapy. Molecular Docking study was done to analyze the protein interaction with Miglustat (ligand), as a result native (3THC) structure had a binding affinity of −8.18 kcal/mol and two variant structures had an average binding affinities of −2.61 kcal/mol (Y83D) and − 7.63 kcal/mol (Y270D). Finally, Molecular Dynamics Simulation was performed to know the mutational activity of the protein structures on Miglustat for 50,000 ps. The Y83D variant showed higher deviation than native protein and Y270D in all trajectory analysis. The analysis was done to the protein structures to check the structural variations happened through simulations. This study aids to understand the most deleterious mutants, the activity of the drug to the protein structure and also gives an insight on the stability of the drug with the native and selected variants.

溶酶体贮积病包括不同形式的常染色体隐性遗传疾病，其中 GM1 神经节苷脂沉积症通过与一系列进行性神经系统表型相关的复杂糖脂的积累进行分类。GM1 神经节苷脂沉着症是一种遗传性疾病，会逐渐破坏大脑和脊髓中的神经细胞（神经元）。GM1 具有三种主要的发病类型，即婴儿型（I 型）、青少年型（II 型）和成人型（III 型）。这项研究提供了一系列计算方法来检查 GLB1 蛋白中发生的突变。最初，突变分析从 689 个氨基酸变体开始，用于基于序列的筛选，并使用相当多的In-silico通过使用标准工具缩小最重要的变体的工具；即进化分析（77个变体）、致病性预测（44个变体）、稳定性预测（30个变体）、生物物理功能（19个变体）和根据蛋白质结构与PDB ID 3THC的结合位点，七个变体（Y83D、Y83H、 Y270S、Y270D、W273R、W273D和Y333H）被缩小。进行基于结构的分析以了解天然蛋白质和变体与 Miglustat 的相互作用特征；这是目前用于替代酶替代疗法的 FDA 药物。进行分子对接研究以分析蛋白质与 Miglustat（配体）的相互作用，结果天然 (3THC) 结构具有 -8.18 kcal/mol 的结合亲和力，两个变体结构的平均结合亲和力为 -2。61 kcal/mol (Y83D) 和 − 7.63 kcal/mol (Y270D)。最后，进行分子动力学模拟以了解 Miglustat 上蛋白质结构的突变活性 50,000 ps。在所有轨迹分析中，Y83D 变体显示出比天然蛋白质和 Y270D 更高的偏差。对蛋白质结构进行分析以检查通过模拟发生的结构变化。这项研究有助于了解最有害的突变体、药物对蛋白质结构的活性，并深入了解药物与天然和选定变体的稳定性。在所有轨迹分析中，Y83D 变体显示出比天然蛋白质和 Y270D 更高的偏差。对蛋白质结构进行分析以检查通过模拟发生的结构变化。这项研究有助于了解最有害的突变体、药物对蛋白质结构的活性，并深入了解药物与天然和选定变体的稳定性。在所有轨迹分析中，Y83D 变体显示出比天然蛋白质和 Y270D 更高的偏差。对蛋白质结构进行分析以检查通过模拟发生的结构变化。这项研究有助于了解最有害的突变体、药物对蛋白质结构的活性，并深入了解药物与天然和选定变体的稳定性。