2020 Denovo tutorial 3 with PDBID 4F4P
I. Focused De Novo Design with PDB 4F4P
This tutorial assumes that you have finished the virtual screening of this system ([1]). We are going to used some of the files generated by the VS toturial.
Fragment Librarie
A focused fragment library will be used in this tutorial, in order to attempt building the same ligand. A focused fragment library can be generated using the same ligand.
Create a new directory for the fragment library.
mkdir fraglib
Inside the fraglib directory create a new input file for fragment generation.
vi fraglib.in
Generate the fragments by calling the input file through DOCK6
dock6 -i fraglib.in -o fradlib.out
Answer the prompted questions interactively using the following lines.
conformer_search_type flex write_fragment_libraries yes fragment_library_prefix fraglib fragment_library_freq_cutoff 1 fragment_library_sort_method freq fragment_library_trans_origin no use_internal_energy yes internal_energy_rep_exp 9 internal_energy_cutoff 100.0 ligand_atom_file (your path for VS docking)/001.files/4f4p_lig_h.mol2 limit_max_ligands no skip_molecule no read_mol_solvation no calculate_rmsd no use_database_filter no orient_ligand yes automated_matching yes receptor_site_file (your path for VS docking)/002.surface_spheres/selected_spheres.sph max_orientations 1000 critical_points no chemical_matching no use_ligand_spheres no bump_filter no score_molecules no atom_model all vdw_defn_file /gpfs/projects/AMS536/zzz.programs/dock6.9_release/parameters/vdw_AMBER_parm99.defn flex_defn_file /gpfs/projects/AMS536/zzz.programs/dock6.9_release/parameters/flex.defn flex_drive_file /gpfs/projects/AMS536/zzz.programs/dock6.9_release/parameters/flex_drive.tbl ligand_outfile_prefix output write_orientations no num_scored_conformers 1 rank_ligands no
Once fragment generation is completed, following files will be generated. (fraglib_linker.mol2, fraglib_rigid.mol2, fraglib_scaffold.mol2, fraglib_sidechain.mol2, fraglib_torenv.dat) You can use the following commands to check the number of fragments in each file.
grep -wc MOLECULE *.mol2
You can also open the mol2 files using chimera and check if the fragments match with the ligand used for fragment generation.
