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A example of the workflow used to complete RFE calculations set up with PMX, run using GROMACS, and analyzed using Alchemlyb

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RFE_example

A example of the workflow used to complete RFE calculations set up with PMX and run using GROMACS

Step 1: Determine you system of interest

For this example we are using a protein - protein binding system although the procedure is essentially the same for a protein ligand system. You will need to obtain starting structures which for this example a crystal structure was available for the protein-protein complex. You then seperate the two moleucles into different PDB files in order to preform the mutations.

Step 2: Generate the hybrid topology

Unless you are intending to examine the mutation on a protein which contains non-standard residues (like phoshorylated residues) you can imply use the PMX webserver to perform the mutations. Alternatively the functions can be downloaded from PMX Github to allow for forcefield modifications.

Step 3: Solvation FE

The solvation FE protocol is outlined above.

Step 4: Complex FE

This step requires repeating the steps associated with the solvation FE with the exception that a complex topology and gro files will need to be generated. The method of generating the complex files will depend on the molecule your protein will be binding.

Step 5: Combine for total FE difference with the mutation

The analysis scripts for generating a value of ΔG for the solvation and complex FE can be found in this repository. The total ΔΔG = ΔG of solvation - ΔG of complex.

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A example of the workflow used to complete RFE calculations set up with PMX, run using GROMACS, and analyzed using Alchemlyb

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