Supplementary data for PTEN project

The current study set out to investigate the effects of harmful nsSNPs on the stability, functionality, and structure of the PTEN. Eleven mutations were identified as potentially affecting the structural and functional characteristics of the PTEN protein: D107N, G129E, S170R, H123R, C124R, R130G, M35R, L70P, R130Q, L112P, H61D, H93R, D252G, G132V, R173C, R173H, and I135T. All 11 changes happened at highly conserved amino acid residue locations, according to the conservation analysis. Conserved domain analysis predicted the loss of domains in M35R and L70P and the loss of catalytic and active sites in C124R, R130G, and R130Q. In molecular dynamic simulation, it can be observed that mutations R173H and C124R consistently exhibit deviation from wild-type PTEN, indicating greater instability in the structure of the protein. Using a variety of computational tools, the in-silico investigation was carried out to shed light on the role missense mutations play in altering proteins.

本研究旨在探究有害非同义单核苷酸多态性（non-synonymous single nucleotide polymorphisms, nsSNPs）对PTEN的稳定性、功能及结构的影响。本研究共鉴定出11个可能影响PTEN蛋白结构与功能特性的突变，具体包括：D107N、G129E、S170R、H123R、C124R、R130G、M35R、L70P、R130Q、L112P、H61D、H93R、D252G、G132V、R173C、R173H及I135T。经保守性分析证实，上述11处突变均位于高度保守的氨基酸残基位点。保守结构域分析预测，M35R与L70P突变会导致对应结构域的缺失，而C124R、R130G及R130Q突变则会造成催化位点与活性位点的丢失。在分子动力学模拟实验中，可观察到R173H与C124R突变始终与野生型PTEN存在结构偏差，提示该蛋白的结构稳定性显著降低。本研究借助多种计算工具开展了计算机模拟（in silico）分析，以阐明错义突变在改变蛋白质结构与功能中所发挥的作用。