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 .
WARNING this should only be done if generating conformations for a very small set of compounds!!! 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
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.
- run OMEGA, but don't ask me how to do that yet.
- 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 natoms nbonds 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:
- furthermore, there will be someothername.nmol2 file which contains the correct partial charges.
- 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 .