2018 Denovo design tutorial 1 with PDB 2NNQ
Contents
2018 Denovo design tutorial 1 with PDB 2NNQ
Files Needed
Fragment Libraries
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.
touch fraglib.in
Generate the fragments by calling the input file through DOCK6
dock6 -i fraglib.in
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 12 internal_energy_cutoff 100.0 ligand_atom_file /Path_to_file/2nnq_lig_withH.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 /Path_to_file/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/parameters/vdw_AMBER_parm99.defn flex_defn_file /gpfs/projects/AMS536/zzz.programs/dock6/parameters/flex.defn flex_drive_file /gpfs/projects/AMS536/zzz.programs/dock6/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) Open the mol2 files using chimera and check if the fragments match with the ligand used for fragment generation.
Focused Denovo Growth
The generated fragments will be used to perform the de novo dock. Here the fragments will added together restricted by different properties like maximum layers, formal charge and molecular weight. Before each connection, DOCK will check with the torsion environment file created in frgment generation to see if that particular connection is seen before. If not the connection won't be made.
Create a new directory for denovo dock.
mkdir denovo
Create a new input file for denovo dock.
touch denovo.in
Run the input file through dock.
dock6 -i denovo.in
Answer the prompted question 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 no ligand_atom_file ./candidate_mol_gen_frag.mol2 limit_max_ligands no skip_molecule no read_mol_solvation no calculate_rmsd no use_database_filter no orient_ligand no bump_filter no score_molecules no atom_model all vdw_defn_file ../../../dock/box/vdw_AMBER_parm99.defn flex_defn_file ../../../dock/dock/flex.defn flex_drive_file ../../../dock/dock/flex_drive.tbl ligand_outfile_prefix output write_orientations no num_scored_conformers 1 rank_ligands no
