Preparing a Membrane-Bound Protein for FEP+

For membrane-bound proteins, the FEP+ panel has an option to run a membrane equilibration protocol. If the system does not have a membrane, it automatically adds a POPC membrane. The option is available in the FEP+ Advanced Options Dialog Box.

Otherwise, if you want to run an FEP+ job on a membrane-bound protein (for example with a different membrane or with a different protocol), follow the steps below to prepare the system.

  1. Prepare the protein with the Protein Preparation Workflow.

    It is recommended that you include a ligand in the preparation, to ensure the binding pocket is not distorted during the membrane relaxation. This ligand does not have to be one that you use for the FEP+ simulations, though it can be.

    See the Protein Preparation Workflow Panel topic and the Protein Preparation Guide — Contents for more information.

  2. Prepare a Desmond model system including the membrane and ligand in the System Builder Panel.

    It is recommended that you use the OPM database if possible, as the proteins are already aligned to the membrane, and this information is used by the System Builder to prepare the model system.

  3. Run a Desmond molecular dynamics simulation to relax the model system, using the Molecular Dynamics Panel.

    By default the Relax membrane model system before simulation is selected: if not, select it. You can run a simulation with the default parameters. This step is optional, as you can run the equilibration protocol as part of the FEP+ job using the option mentioned above.

  4. Convert the output from the system builder or the membrane relaxation simulation for use with FEP+:

    $SCHRODINGER/run membrane_cms2fep.py -o output_pv.mae relax-jobname/relax-jobname-out.cms

    The name of the input file is determined by the name of the Desmond job that was run for the relaxation.

  5. If you added a ligand in the preparation (as recommended in Step 1), you must remove it from the receptor entry in the pose-viewer file, output_pv.mae.

You can then import the output pose-viewer file, output_pv.mae, into the FEP+ panel in Maestro.