Preparing the ligand

Preparing a ligand

Automatic way, starting from SMILES

This way, you will make use of John's automatic scripts for database preparation and actually upload new molecules to a special section of ZINC.

• it is advisable to create a special subdirectory, since many new files will be generated.
• the file containing the SMILES strings should contain a string followed by an identifier on each line.
• OPTIONAL: run convert.py --i=yourname.smi --o=yourname.ism . This will convert your SMILES to isomeric SMILES.
• run dbgen.csh yourname.smi.
  • Note that the dbgen.csh does not work for more that 1000 molecules.
  • Brake up your molecules into chunks of 1000 and run dbgen on each chunk.
  • Clean up your directory afterwards. dbgen.csh generates a lot of files that you do not need if it ran correctly.
• you should obtain a file somename.db.gz .

optional

To increase the number of molecules that are written out for the database generation, copy the file $DOCK_BASE/data/omega.parm into the directory that dbgen.csh is going to be run in.

• At the end of the omega.parm file you will see a section called "Torsion Driving Parameters", here you will find three variables that can be changed.
  • • SetMaxConfs(600) #set to higher numbers ie. 1000
    • SetRMSThreshold(0.80) #set to lower numbers ie. 0.50
    • SetEnergyWindow(12.5) #can be changed but this can often generate broken molecules
• WARNING this should only be done if generating conformations for a small set of compounds!!!

Manual way

Isolating the ligand as .mol2 file

• extract the ligand structure from the .pdb file.
• assign hydrogens.
• assign all atom (Sybyl/TAFF) and bond types.
• save it as ligandname.mol2 file.

Running omega

• run OMEGA, but don't ask me how to do that yet.

Running amsol

• find more information about amsol on its homepage.
• mkdir ./amsol2
• Use file2file.py to get the right formal charge to feed to AMSOL. It is also important to change the name, otherwise the original .mol2 file will be overwritten!

file2file.py -g ligandname.mol2 ./amsol2/someothername.mol2

• edit ./amsol2/someothername.mol2 :
• delete all lines prior to @<TRIPOS>MOLECULE
• change line 2 (molecule name) to something of the format ABCD12345678 (four capital letters followed by eight numbers).
• line 3 should be n_atoms n_bonds 0 0 0
• the @<TRIPOS>MOLECULE section must consist of exactly 5 lines (adjust by adding/deleting blanks).
• remove all sections after the @<TRIPOS>BOND section.
• delete the blank lines between the ATOM and BOND sections, if there are any.
• run RunAMSOL3.csh WAIT
• the output someothername.solv file will contain the following:

AMSOL output

line #1	molname	<math>n_{atoms}</math>	charge	pol_solv	?	apol_solv	total_solv
other lines	charge	pol_solv	?	apol_solv	total_solv
(per_atom)

• furthermore, there will be someothername.nmol2 file which contains the correct partial charges.

Running mol2db

• edit someothername.nmol2 so that the @<TRIPOS>MOLECULE section consists of exactly 6 lines.
• edit the inhier file so that the 'mol2_file', 'db_file' and 'solvation_table' entries are correct.
• run mol2db inhier
• add the preamble at the top of the file.
• gzip the resulting file so that it can be used by DOCK .