Automated Fragmentation¶

ORCA features a very versatile fragmentation algorithm called Fragmentator. Even though it is mainly designed for treating large biochemical systems like proteins, the user has full control over the fragmentation schemes. In this context, custom fragment libraries can be defined or native libraries and fragmentation procedures can be used.

The fragmentation can be controlled via the %frag block and a respective fragmentation procedure is defined via FragProc. StoreFrags true can be used to save the generated fragments in XYZ format in a basename.fragments.xyz file.

%frag
   FragProc Connectivity
   StoreFrags true
end

Note

Some native libraries may be too specialized for general use, therefore it is typically recommended to tailor the fragment library to any specific requirements.

Hint

If you want to only check the fragments, a full SCF calculation can be avoided by additionally defining DryRun true within the %scf block.

Example 1: Fragmentation of Sulfociprofloxacin¶

Ciprofloxacin is a potent broad-spectrum antibiotic belonging to the fluoroquinolone group. In this example, we will employ the automatic fragmentation tool of ORCA with a custom fragment library to the Ciprofloxacin derivative Sulfociprofloxacin (PubChem: 128781) which carries many different functional groups.

../_images/128781_sulfociprofloxacin.png — Figure: Molecular structure of sulfociprofloxacin extracted from the PubChem database.¶

First, we start to create our own tailored fragment library that can be used for similar compounds or substituent classes afterwards. For this, we use Avogadro 2 or any other molecular builder to extract the fragment geometries and create a library file CustomLib.xyz.

This file contains the Cartesian coordinates of the fragment in XYZ format, charge, multiplicity, and a name for the fragment. The correct assignment of charge and multiplicity is important for automated tasks like energy decomposition calculations that make use of the respective fragment definitions.

   1
CHARGE -1 MULT 1 NAME FLUORIDE
F     -0.9737000000    2.9130000000    0.3523000000
   8
CHARGE 0 MULT 2 NAME CYCLOPROPYL
H      0.4734000000   -4.0509000000    0.0656000000
H      0.9294000000   -2.8692000000    1.3726000000
H      2.0343000000   -2.9655000000   -1.5480000000
C      2.1615000000   -2.7286000000   -0.4964000000
C      2.6590000000   -3.8213000000    0.3905000000
C      1.2259000000   -3.3823000000    0.4658000000
H      3.2982000000   -3.5739000000    1.2291000000
H      2.8686000000   -4.7831000000   -0.0614000000
   5
CHARGE 0 MULT 2 NAME SO2OH
S     -6.4630000000   -0.3132000000   -0.0993000000
O     -7.0642000000    0.4318000000   -1.1888000000
H     -6.5219000000    1.4414000000    1.2900000000
O     -6.7763000000    0.4890000000    1.2850000000
O     -6.8022000000   -1.7074000000    0.1135000000
[...]

Now we can start the fragmentation of our example molecule using the %frag block. As we want to use our customized fragment library, we define FragProc Extlib and provide the name of our library file via XZYFRAGLIB "CustomLib.xyz". To not perform a full DFT calculation, we make use of the DryRun true setting within the %scf block.

!PBE def2-SVP

%scf
   DryRun true
end

%frag
   PrintLevel 3
   StoreFrags true
   FragProc Extlib
   XZYFRAGLIB "CustomLib.xyz"
end

*xyzfile 0 1 sulfociprofloxacin.xyz

By setting StoreFrags true, we saved all identified fragments in a multixyz file basename.fragments.xyz. Further, all identified fragments are documented in the ORCA output file basename.out.

================================================================================
 STARTING AUTOMATIC FRAGMENTATION:
===================================================
  PrintLevel: 3
  XZYFragLib: CustomLib.xyz,
  Inter. Frag. Bonds: NO
  BoxSize: 10.00 a.u.
  DistCutOff:  5.00 a.u.
  Fragmentation Procedure: Orca_input,
                           Ext_lib,
                           Not_assigned
===================================================

===================================================
Tfragmentator: Fragmenting by Orca_input
===================================================
 No New Fragments Assigned

 Orca_input fragmentation done in            0.000 Sec.
===================================================
Tfragmentator: Fragmenting by Ext_lib
===================================================
****
**** There are 5 Ref structures found in file CustomLib.xyz
****

------------------------------------------
 Match: 1, Assigned Fragment: 1
------------------------------------------
  Name:  FLUORIDE Method: Ext_lib
[...]

We can now visualize our fragments file with ChimeraX to get a visual picture of the identified fragments. Note that the fragmentation algorithm grouped the central aromatic moiety as it did not match any predefind fragment.

../_images/128781_sulfociprofloxacin_fragments.png — Figure: Overlay of sulfociprofloxacin and the identified fragments (space-filling model).¶

Example 2: Mixing of Fragmentation Procedures¶

To show the transferability of our custom fragment library created in Example 1, we will now employ it to an arbitrarily substituted benzene coordinated by a DMSO solvent molecule.

../_images/arbitrary.png — Figure: Molecular structure of an arbitrary benzene derivative with DMSO solvent.¶

Within the Fragmentator it is possible to mix various fragmentation procedures. In this case we also want to create a fragment for the non-covalently bound solvent DMSO molecule. Therefore, we will add the native FragProc Solvents that covers most common solvent molecules.

!PBE def2-SVP

%scf
   DryRun true
end

%frag
   PrintLevel 3
   StoreFrags true
   FragProc Extlib, Solvents
   XZYFRAGLIB "CustomLib.xyz"
end

*xyzfile 0 1 structure.xyz

We can now see that the Fragmentator successfully created the fragments previously defined in our custom fragment library and also identifies the DMSO solvent molecule as individual fragment.

../_images/arbitrary_fragments.png — Figure: Overlay of the arbitrary benzene derivative and the identified fragments (space-filling model).¶

Automated Fragmentation¶

Example 1: Fragmentation of Sulfociprofloxacin¶

Example 2: Mixing of Fragmentation Procedures¶

Structures¶