Using QCG on protein solvation

[lynn-gu]

Hi Crest team,

I'm working on a project on protein desiccation which involves solvation of a single protein molecule in very small number of water molecules. I tried running QCG on the protein but I didn't get any results and the output .xyz file is empty. I have attached my output and 1pga.xyz is the protein. It is a very small protein with 55 amino acids.

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       ║          | (__|   / _|\__ \ | |            ║
       ║           \___|_|_\___|___/ |_|            ║
       ║                                            ║
       ║  Conformer-Rotamer Ensemble Sampling Tool  ║
       ║          based on the xTB methods          ║
       ║                                            ║
       ╚════════════════════════════════════════════╝
       Version 3.0, Sat Apr  6 18:06:37 UTC 2024
       commit (d321183) compiled by 'runner@fv-az778-216'

   Cite work conducted with this code as

   • P.Pracht, F.Bohle, S.Grimme, PCCP, 2020, 22, 7169-7192.
   • S.Grimme, JCTC, 2019, 15, 2847-2862.
   • P.Pracht, S.Grimme, C.Bannwarth, F.Bohle, S.Ehlert,
     G.Feldmann, J.Gorges, M.Müller, T.Neudecker, C.Plett,
     S.Spicher, P.Steinbach, P.Wesołowski, F.Zeller,
     J. Chem. Phys., 2024, 160, 114110.

   for works involving QCG cite

   • S.Spicher, C.Plett, P.Pracht, A.Hansen, S.Grimme,
     JCTC, 2022, 18 (5), 3174-3189.
   • C.Plett, S. Grimme,
     Angew. Chem. Int. Ed. 2023, 62, e202214477.

   for works involving MECP screening cite

   • P.Pracht, C.Bannwarth, JCTC, 2022, 18 (10), 6370-6385.

   Original code
     P.Pracht, S.Grimme, Universität Bonn, MCTC
   with help from (alphabetical order):
     C.Bannwarth, F.Bohle, S.Ehlert, G.Feldmann, J.Gorges,
     S.Grimme, C.Plett, P.Pracht, S.Spicher, P.Steinbach,
     P.Wesolowski, F.Zeller

   Online documentation is available at
   https://crest-lab.github.io/crest-docs/

   This program is distributed in the hope that it will be useful,
   but WITHOUT ANY WARRANTY; without even the implied warranty of
   MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
   GNU Lesser General Public License (LGPL) for more details.

 Command line input:
 $ /home/mgcf/software-ws/xtb/crest 1pga.xyz --qcg water.xyz --nsolv 40 --gfnff - -T 16 --alpb water

  --gfnff : Use of GFN-FF requested.
  -T 16 (CPUs/Threads selected)
  --alpb water : implicit solvation

> Setting up backup calculator ... done.
 ----------------
 Calculation info
 ----------------
> User-defined calculation level:
 : GFN-FF calculation via GFNFF lib
 :   Molecular charge    : 0
 :   Solvation model     : alpb
 :   Solvent             : water
 :   Weight              : 1.00000


  ========================================
  |           ----------------           |
  |                 Q C G                |
  |           ----------------           |
  |        Quantum Cluster Growth        |
  |       University of Bonn, MCTC       |
  ========================================
   S. Grimme, S. Spicher, C. Plett.

   Cite work conducted with this code as

   S. Spicher, C. Plett, P. Pracht, A. Hansen, S. Grimme, JCTC, 2022, 18, 3174-3189.


   The use of the aISS algorithm is requested (recommend).
   This requires xtb version 6.6.0 or newer.
   xTB-IFF can still be used with the --xtbiff flag.


  =========================================
  |   quantum cluster growth: INPUT       |
  =========================================

  QCG: Only Cluster Generation

  input parameters
  solute                 : 1pga.xyz
  charge                 : 0
  uhf                    : 0
  solvent                : water.xyz
  # of solvents to add   : 40
  Cluster generated that are above 10 % populated
  # of CPUs used         : 16
  Solvation model        : water
  xtb opt level          : normal
  System temperature [K] : 298.1
  RRHO scaling factor    : 0.75


 Solute geometry
  molecular radius (Bohr**1):   22.86
  molecular area   (Bohr**2):19686.41
  molecular volume (Bohr**3):50062.43
 Solvent geometry
  molecular radius (Bohr**1):    3.87
  molecular area   (Bohr**2):  194.47
  molecular volume (Bohr**3):  243.48

  radius of solute    :    36.86
  radius of solvent   :     6.24

  =========================================
  |            Preoptimization            |
  =========================================
  Total Energy of solute:     -90.1581918 Eh
  Total energy of solvent:     -0.3276560 Eh

  ________________________________________________________________________

  __________________     Solute Cluster Generation   _____________________

  ________________________________________________________________________


  =========================================
  |   quantum cluster growth: GROW        |
  =========================================


  Water as solvent recognized,  adjusting scaling factor for outer wall pot to 0.80

  Constraining solute during Growth
 Solute:
       unit ellipsoid axis a,b,c     :   0.370   0.319   0.312
 Solvent:
       unit ellipsoid axis a,b,c     :   0.384   0.323   0.292

  solvent anisotropy            :     1.130
  solute anisotropy             :     1.084
  roff inner wall               :    54.259
  solute max dist               :    70.659
  solvent max dist              :     7.296
  inner unit axis               :     0.408     0.303     0.290
  inner ellipsoid/Bohr          :   104.090    77.193    73.897
  scaling factor outer ellipsoid:     0.800
  outer ellipsoid/Bohr          :    71.908    61.925    60.588

  Size       E        De       Detot      Density     Eatom    av. R  Rlast   Volume    Opt
            [Eh]    [kcal]     [kcal]     [u/Å^3]     [kcal]   [bohr] [bohr] [bohr^3]
   Wall Potential too small, increasing size by 5 %
   New scaling factor 0.84
   Wall Potential too small, increasing size by 5 %
   New scaling factor 0.88
   Wall Potential too small, increasing size by 5 %
   New scaling factor 0.93
   Wall Potential too small, increasing size by 5 %
   New scaling factor 0.97
   Wall Potential too small, increasing size by 5 %
   New scaling factor 1.00

I haven't seen examples of QCG used on a protein scale. Is there an upper limit to how large the solute molecule can be in QCG? I feel that the scaling factor is still too small for my application, is there any way to override the default maximal scaling factor of 1?

[cplett]

Hi,
The default scaling factor can be adjusted with the --wscal <Real> command, where <Real> is the scaling factor. You might start with a value like 1.5 and check if the result aligns with your expectations.
If the issue persists even with larger factors, it might also indicate that xtb does not work properly. This was the case for xtb version 6.7.1, so if you are using that version, I recommend switching to a current bleeding-edge version or version 6.7.0.