Using the SwissParam Webserver

1. Checking that the server is up and running

If the Web server is up and running, you will receive a "Hello World!" message. If not, please contact the SwissParam team.

2. Starting a parameterization

a. Non covalent small molecule

You can launch the parameterization by using the following command:
where:

• molecule.mol2 is the mol2 file of the small molecule and can have any name
• approach is the approach used to parameterize.

Available approaches are:
both (default), mmff-based, match

Note: when using the mmff-based approach, it is possible to use CHARMM22/27 instead of CHARMM36 to generate the parameters. For that, simply add "&c22" or "&c27" to your command-line.

If your Mol2 does not contain hydrogens, you can add the "addH" option to the command-line, it will protonate the molecule at pH 7.4:
If you want to use a SMILES instead of a Mol2 file: If no problem was found, the calculation is submitted to the queue of the server. Then, the user is provided with a randomly chosen Session Number. This Session Number will allow the user to check what is the status of the calculation, and later retrieve the results in case of a successful calculation.

Example: to run a parameterization with GF1.mol2, you must write: Here, 65720367 is the Session Number of the submitted parameterization.

b. Covalent small molecule

To parameterize a covalent small molecule, use the following command and specify some arguments: where:

• molecule.mol2 is the mol2 file of the small molecule and can have any name
• ligsite is the ligand site (atom name) of the covalent link
• reaction is the reaction namespace
• protres is the protein residue doing the covalent link, it can be CYS, SER, LYS, ASP, GLU, THR, TYR
• topology is the topology of your ligand (post-cap or pre reactive).

Available reactions are:

• aziridine_open: ring-opening mechanism on aziridine
• blac_open: ring-opening mechanism on β-lactam
• carbonyl_add: addition on carbonyl
• disulf_form: formation of a disulfide
• epoxide_open: ring-opening mechanism on epoxide
• glac_open: ring-opening mechanism on ɣ-lactam
• imine_form: formation of imine.
• michael_add: addition on Michael-like acceptor
• nitrile_add: addition on nitrile
• nucl_subst: nucleophilic substitution

Example: to run a parameterization with 92V.mol2, where the ligand site is S24, the protein residue is CYS, the reaction is disulf_form, and the topology is post reactive, you must write: The approach used will automatically be MMFF-based.
Note: it is possible to use CHARMM22/27 instead of CHARMM36 to generate the parameters. For that, simply add "&c22" or "&c27" to your command-line.

You can then check your session status using the session number you received upon submission.

Note: when using the post topology it is possible to specify which atoms must be deleted to get the pre topology. In case these atoms do not have an "official PDB name", specify them by adding "&delete=atom1,atom2".
For example, with CB0000002.mol2:

3. Checking the status of a parameterization

You can check the status of the job using the Session Number that you have received upon submission. If the calculation is pending in the queue waiting for its turn, you will be informed about that, and you will be provided with the number of jobs that are waiting before it in the queue. If the job is currently running, you will be informed about that and the running time will be reported. If the parameterization is over, you will be also informed that the job is finished.

4. Cancelling a parameterization

You can cancel the parameterization that is currently running or pending in the queue. The following command will remove the calculation from the queue of the server:

5. Retrieving the results of a parameterization

After you have confirmed that your submitted job is finished (see above), you can retrieve the results: Simply run the given command to retrieve your results:
You will download the gzip results file on your machine.