Maestro

Maestro is a part of the Schrödinger program suite.
However, in variance to most of the other programs, it is free to academic users (but then, you cannot fill in missing residues or predict pKa values of ligands).
Ensure that you download it from https://www.schrodinger.com/freemaestro.

The current version is Maestro 2020-1.
The files are located in /temp4/bio/Schrodinger/Maestro-2020-1 and it is run by maestro.
However, currently it seems to work only if you have own your own installation (available also for Mac and PC laptops), i.e. you need to run the current installation as user bio.

Set
export SCHRODINGER=/temp4/bio/Schrodinger/Maestro-2020-1
export SCHRODINGER_PYTHONPATH=""
alias maestro=$SCHRODINGER/maestro
and then run the program with
maestro

You get a number of warnings, but the program seems to work

Protein setup

Maestro is particularly strong for the setup of a new protein and this is currently our prime use of the program.
Below, I describe a tentative scheme for the setup of a new protein structure, using a combination of Maestro and our local programs.

  1. Keep thorough notes on all you done with the file (e.g. flipped or deleted groups).

  2. Click on the Prep Wiz (protein preparation wizard).

  3. Open the desired PDB file by giving the ID or browsing the correct file.
    Coloured groups are HET compounds or problems.

  4. Uncheck "Delete waters beyond 5 Å" and then hit Preprocess.
    It takes ~1 minute.

  5. Review the "Problems" "Current overlapping atoms" box.
    Too close H atoms will probably solve later on.

  6. Review the "Problems" "Alternate positions" box.
    By "Next position" you can see the other position
    By "commit" you select one configuration.

    This part is probably better run or at least checked by changepdb, command occ

  7. Go to the "Review and Modify" side and click "Analyze Workspace"
    Possibly delete subunits and Het groups by clicking on the and the on Delete.

  8. Save a pdb file with export command.

  9. Go to the "Refine" side and click on "Optimize"
    This may take several hours as all proton positions are optimised.

  10. While running, run propKa, note the pKa of the His residues, and check if any of the Asp and Glu have a pKa above 7 or any Lys, Arg, and Tyr have pKa below 7.

  11. Run changepdb, command hi to analyse the His residues.

  12. Run changepdb, command bc to find all buried charges.
    Find all ionic pairs and note what buried charges are not involved in ionic pairs.

  13. Check all these with rasmol or similar. There should be no buried charges, not involved in ionic pairs, except close to metal ions.

  14. With all this information, decide the protonation of all His, Asp, Glu, Lys, and Arg residues.

  15. When Maestro is finished, click on "Interactive Optimizer" and then on "Analyze Network"
    Again, it may take many minutes.

  16. When finished, you may go through all Asn and Gln group to see which may be flipped.

  17. Likewise, you should check for each His residue the protonation state, considering 6 possible states.
    With the information from changepdb, decide the actual protonation state and check the lock box for all these.
    Also enforce possible unusual protonation state of other residues.

  18. Finally, click "Optimize".
    This may again take hours.

  19. Save the pdb file.
    Note that HID/E/P, ASH, GLH, LYN, and ARN need to be set by hand afterwards.

  20.  Load the file into amber with tleap, as described in the equilibration page.


Add protons to a ligand
  1. Import the pdb file (File - Import Structures)
  2. Mark each double / conjugated bond
  3. Right click and select Increase bond order (C atoms are then protonated)
  4. Repeat 2-3 for all bonds.
  5. Selet all  (Ctrl-A)
  6. Edit - Add Hydrogens
  7. File - Export structure