Using CHARMM-GUI Solution Builder

Hello! This is an updated entry for using the CHARMM-GUI solution builder, specifically for the COVID-19 project. This entry is intended to be as general as possible. Step-by-step instructions specific to using CHARMM-GUI to insert CFTR structures into a lipid bilayer can be found here.

NOTE: You can find exactly how I used CHARMM-GUI to generate files for the Free Decoy (to be utilized for GROMACS benchmarking) here, with screenshots. Specific instructions for using and benchmarking GROMACS can be found here.

NOTE 2: If you're using this page for designed decoys, an exact guide for how I plugged in the appropriate data can be found here. You'll want to mimic that procedure pretty much exactly. I included screenshots in case you're confused.

Getting to the Solution Builder

CHARMM-GUI has several components. For COVID-19 research, we're mostly using the solution builder. To get there, use this link, or go to charmm-gui.org and use the toolbar at the left to navigate to Input Generator > Solution Builder.

You may need to make an account. It is safe to do so, as well as helpful. An account allows you to retrieve in progress jobs if something goes wrong with your browser mid-generation.

Step 1

Step one allows you to choose the PDB file you intend to use. Upload the Modeller .pdb file, and be sure to select the .PDB option.

Step 2

Here, you'll select the model and atoms you want to include in the waterbox, as well as the section of the chain you want to include. To do that, check and uncheck the boxes as indicated, and change the numbers in Residue ID as necessary. The Modeller files are all clean, so you shouldn't leave anything out.

Step 3

Often, you'll be able to leave this as the default settings. Be sure to check the disulfide bond settings, and don't model missing residues. Use the hints above the table on the COVID-19 Progress page to mark the appropriate disulfide bonds if not already done for you. sACE2 and the RBD should each have disulfide bonds, so if Disulfide Bonds is not checked on those systems, you need to fix it!

Step 4

This is where you'll set the options for the solution. You can specify the waterbox size or fit it to the protein. For the COVID-19 project, the edge distance should be at least 10 (in Å). Depending on your purpose, the waterbox type could be anything, but use the highest-dimension shape possible to reduce calculation times (a dodecahedron has 70% of the volume of a cube, and thus takes less time to simulate). You can also select the ions you want to include in the solution; use 0.142 M NaCl. Important: CHARMM-GUI has been updated. You will need to add NaCl to the system, delete KCl, change the concentration of NaCl to 0.142 M, then press the Calculate button before continuing.

Step 5

There has not yet been a case where I haven't been able to let CHARMM-GUI set the grid automatically, so leave this as the default unless you know you can't.

Step 6

Here, you choose the force field options and select the programs for which you need input. For molecular modeling, we use GROMACS, so check that box. You can also change the temperature of the system at the bottom of this page; set it to 310 K (roughly body temperature).

Step 7

You download the files on this page. You'll need to click download.tgz at the top right corner of the main box to get the file. Depending on your operating system, different things will happen to the file automatically — some may change the extension, some may decompress it automatically, and some may not be able to do anything with it at all.

Once this is done, upload the CHARMM-GUI files to the Drive and link them on the COVID-19 Progress page.