DOI: 10.5061/dryad.547d7wmkq
title: Computational data for: Mutations in Mig6 reduce inhibition of the epidermal growth factor receptor

description: 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.
description: # 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
 equilibrating models 3. `03_production`: input and output files for
 production MD for only first seed (6 seeds total) #### `01_prep` folder
 contents Here, `01_prep` contains the prepared models for the solvated
 (`wet`) and unsolvated (`gas`) in the form of `.prmtop` and `.rst7` files.
 1. `4zjv.gas.complex.prmtop`: Topology for gas-phase complex 2.
 `4zjv.wet.complex.prmtop`: Topology for solvated complex 3.
 `4zjv.gas.complex.rst7`: Coordinates and velocities for gas-phase complex
 4. `4zjv.wet.complex.rst7`: Coordinates and velocities for solvated
 complex #### `02_equi` folder contents Here, `02_equi` contains the input
 and outputs of the 9-step equilibration and minimization protocol. Please
 refer to the original work in Table 1. The folder will contain five file
 types: * `.info` – Metadata or descriptive information * `.mdin` – Input
 parameters for the MD simulation * `.mdout` – Output logs from the MD run
 * `.rst7` – Restart files containing updated coordinates * `.trj` –
 Trajectory files storing atomic positions during simulation Each file will
 have the protocol step number, min or equi tag, and the file type embbeded
 into the file names. **Naming convention**: Each file includes the step
 number, the type of step (`min` for minimization or `equi` for
 equilibration), and the file type. For example: * `01.min.trj` →
 Trajectory file from step 1 (minimization) * `03.equi.mdout` → Output log
 from step 3 (equilibration) For example: `01.min.trj` means step one in
 the protocol (`01`), where it is the minimization (`min`) and its a
 trajectory file. (`.trj`) #### `03_production` Here, we have five files
 for the first seed of the production MD simulation. * `prod1.info` –
 Descriptive info about this production run - `prod1.mdin` – Input
 parameters for production MD - `prod1.mdout` – Output log - `prod1.rst7` –
 Final restart file - `prod1.trj` – Trajectory of the MD simulation ##
 Software Used The simulations and data were generated using tools from the
 AMBER22 software suite: ``` tleap – for system preparation ``` ```
 pmemd.mpi – for running the MD simulations in parallel ``` Both programs
 are included in the AMBER22 package. ## Access information Data was
 derived from the following sources: * We used pdb system
 [4ZJV](https://www.rcsb.org/structure/4ZJV) to prepare the wildtype and
 mutated models.