View source for 2020 Denovo tutorial 1 with PDBID 3VJK

In a previous tutorial, we conducted virtual screenings of molecules from a small library. This means that we were identifying previously made compounds that can potentially bind the receptor. In this De Novo design, fragments of molecules are used to generate novel compounds. This can be beneficial for discovering new lead compounds--however-- there are two major drawbacks. First, it can be computationally expensive to do De Novo design. The second drawback is that the compound that is generated from using a De Novo method may not be possible to synthesize. 
==I. Focused De Novo==
Rather than generating a large fragment library. We will be generating fragments of our original ligand. 
===Fragment library Generation===
The first step is to make a new directory for the fragment library. 
   mkdir 015.fraglib 
Next, we will make an input file for dock 
   vim fraglib.in
It will contain the following:
  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                                yes
  use_internal_energy                                          yes
  internal_energy_rep_exp                                      12
  internal_energy_cutoff                                       100.0
  ligand_atom_file                                             ./../001.build/3VJK_ligand_hydrogens.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                                           ./../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
Now you will be able to run dock
   dock6 -i fraglib.in 
You should have generated the following files:
   fraglib_linker.mol2  fraglib_rigid.mol2  fraglib_scaffold.mol2  fraglib_sidechain.mol2  fraglib_torenv.dat  output_scored.mol2
These fragments should match up with the ligand that was used to generate the library.

=Focus Denovo=