Computational data for: Mutations in Mig6 reduce inhibition of the epidermal growth factor receptor

Mitogen-inducible gene 6 (Mig6) is a cellular inhibitor of epidermal growth factor receptor (EGFR) that binds directly to the EGFR kinase domain and interferes with signaling. Reduced Mig6 expression is correlated with increased EGFR activity in multiple cancer models. Here, we investigated whether disease-associated point mutations could reduce the inhibitory potency of Mig6. We show that several cancer-associated mutations, and a mutation derived from Alzheimer's Disease patients, diminish the ability of Mig6 to bind and inhibit EGFR in vitro. In mammalian cells, the mutations decreased the Mig6-induced suppression of basal and EGF-stimulated autophosphorylation, MAP kinase phosphorylation, and cell migration. To probe the mechanisms by which the mutations could lead to reduced Mig6 inhibition, we constructed atomic-level computational models of Mig6 complexed with the EGFR catalytic domain and performed molecular dynamics simulations for wild-type and mutant complexes., , # Computational data for: Mutations in Mig6 reduce inhibition of the epidermal growth factor receptor

## Description of the data and file structure

Atomic-level AMBER program (version 22) input and output files are provided for molecular dynamics (MD) setups and simulations of MIG6 (wildtype, G334R, S390N, and P377S variants) complexed EGFR and solvated in TIP3P water. In this repository, there are four mutations of pdb [4ZJV](https://www.rcsb.org/structure/4ZJV) used for the corresponding work.

### Files and variables

#### Download folder structure

Each `tar.gz` folder represents one of the four mutations.

1. wild-type or `no_mut.tar.gz`
2. G344R mutation or `G344R_mut.tar.gz`
3. S390N mutation or `S390N_mut.tar.gz`
4. P377S mutation or `P377S_mut.tar.gz`

#### Folder structure for each download `xxx.tar.gz` folder

Each `xxx.tar.gz` contains three folders:

1. `01_prep`: prepared models for modeling using equilibration and production MD
2. `02_equi`: input and output files for ...,

丝裂原诱导基因6（Mitogen-inducible gene 6, Mig6）是表皮生长因子受体（epidermal growth factor receptor, EGFR）的细胞内抑制剂，可直接结合EGFR激酶结构域并干扰其信号传导通路。Mig6表达水平降低与多种癌症模型中EGFR活性升高显著相关。本研究旨在探究疾病相关点突变是否会减弱Mig6的抑制效力。实验结果表明，多个癌症相关突变以及源自阿尔茨海默病患者的突变，均可在体外削弱Mig6结合并抑制EGFR的能力。在哺乳动物细胞中，上述突变会减弱Mig6介导的对基础状态及表皮生长因子（EGF）刺激下的自身磷酸化、丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）磷酸化以及细胞迁移的抑制作用。为了阐明此类突变导致Mig6抑制活性降低的分子机制，我们构建了Mig6与EGFR催化结构域结合的原子级计算模型，并对野生型及突变型复合物开展了分子动力学（molecular dynamics, MD）模拟。

# 配套计算数据：Mig6突变减弱对表皮生长因子受体的抑制作用

## 数据与文件结构
本数据集提供了用于MIG6（野生型、G334R、S390N及P377S变体）与EGFR复合物的分子动力学（MD）构建与模拟的AMBER程序（版本22）原子级输入与输出文件，该复合物采用TIP3P水模型进行溶剂化。本仓库中使用了来自PDB [4ZJV](https://www.rcsb.org/structure/4ZJV)的四种突变体开展对应研究。

### 文件与变量

#### 下载文件夹结构
每个`tar.gz`文件夹代表四种突变体之一：
1. 野生型，即`no_mut.tar.gz`
2. G344R突变体，即`G344R_mut.tar.gz`
3. S390N突变体，即`S390N_mut.tar.gz`
4. P377S突变体，即`P377S_mut.tar.gz`

#### 单个下载`xxx.tar.gz`文件夹内部结构
每个`xxx.tar.gz`压缩包包含三个子文件夹：
1. `01_prep`：用于建模、平衡模拟及生产性分子动力学模拟的预处理模型
2. `02_equi`：用于……的输入与输出文件