These data/instructions acompany the folowing manuscript:
Title: Membrane mediated mechanical stimuli produces distinct active-like states in the AT1 receptor.
Authors:Bharat Poudel (University of Vermont), Rajitha Rajeshwar T. (University of Vermont), Juan M. Vanegas (Oregon State University)
Pre-print: https://www.researchsquare.com/article/rs-2106113/v1
Each folder contains the input data generated from the MD simulations, the python script used to generate the corresponding plot, and the final png image. Each data file has a header that describes each column in the file.
Statistical analyses including mean, standard deviation, quartiles, etc. calculated within the python scripts based on the input data files.
The folder MD_configurations contains the initial and final configurations for all the simulations presented in the study. The files are organized into folders labeled System_#. The system description is shown in the table below and also inside a README.md file in each folder.
| System | Total Nr. of Atoms | Box dimensions (nm) | Nr. of Lipids | Nr. of Waters | Cl- | Na+ |
|---|---|---|---|---|---|---|
| (1) DMPC + AT1R | 99,132 | 10x10x11.8 | 300 | 27,388 | 13 | 0 |
| (2) POPC + AT1R | 112,330 | 10.4x0.4x13.5 | 304 | 31,068 | 13 | 0 |
| (3) SOPC + AT1R | 106,560 | 10.4x10.4x13.5 | 298 | 29,050 | 13 | 0 |
| (4) SOPC:SOPE + AT1R | 90,885 | 9.5x9.5x13 | 300 | 23,789 | 13 | 0 |
| (5) SOPC + AT1R + AngII | 106,662 | 10.4x10.4x13.5 | 298 | 29,050 | 13 | 0 |
| (6) SOPC + AT1R + S1I8 | 106,651 | 10.4x10.4x13.5 | 298 | 29,050 | 14 | 0 |
| (7) SOPC + AT1R + S1I8 +Nb | 107,821 | 10.4x10.4x13.5 | 298 | 29,056 | 8 | 0 |
| (8) SOPC + AT1R + Nb | 107,912 | 10.4x10.4x13.5 | 298 | 29,056 | 7 | 0 |
| (9) POPC + F309P/313P AT1R | 82,319 | 10.4x10.4x10 | 304 | 21,071 | 13 | 0 |
| (10) SOPC + F309P/313P AT1R | 83,329 | 10.5x10.5x11 | 298 | 21,313 | 13 | 0 |
| (11) SOPC:SOPE + F309P/313P AT1R | 72,427 | 9.5x9.5x10 | 300 | 17,643 | 13 | 0 |
| (12) POPC + AT1R (C36/Anton) | 49,146 | 6.4x6.4x11.6 | 100 | 10,154 | 39 | 26 |
| (13) SOPC + AT1R (C36/Anton) | 52,021 | 6.4x6.4x12.5 | 100 | 10,911 | 41 | 28 |
| (14) SOPC + AT1R + AngII (C36/Anton) | 48,274 | 6.7x6.7x11.5 | 100 | 9,616 | 37 | 24 |
Compiling and installing the PLUMED-patched version of GROMACS
The source code for GROMACS can be downloaded from https://manual.gromacs.org/2019.6/download.html. PLUMED can be downloaded from https://www.plumed.org/download. The particular version of PLUMED used for this study can be found in the following git repository: https://github.com/vanegasj/plumed2.
Installation instructions for compiling and installing PLUMED can be found here: https://www.plumed.org/doc-v2.7/user-doc/html/_installation.html. This page also contains instruction on how to patch GROMACS with PLUMED. Once the GROMACS code has been patched, you can proceed with the normal compilation and installation of GROMACS
Free energy of AT1 receptor with partial agonist (S1I8)
The folder S1I8_example_fes contains contains the necessary files to reproduce the well-tempered metadynamics free energy calculation shown in Figure 7c of the manuscript. The file run_metad_sim.sh contains the GROMACS command to launch the WT-metadynamics run with the 8 walkers. The folder S1I8/reweight contains the combined colvar files and plumed input files to perform the re-weighting and produce the 2D FES data. The script S1I8_example_fes/reweight/calc_fes.sh will execute the combining procedure and perform the re-weighting using plumed.