5. ligand

This task is used to treat ligand, giving an initial guess for ligand and parameters.

Hint

For a practical way to compute charges, please refer to Tutorial 2: Ligand Preparation.

5.1. Arguments

-i, --in

Mandatory	Yes
Argument	PDB filename or XYZ filename
Default	None

Give the input molecule.

-o, --out

Mandatory	No
Argument	A filename prefix
Default	None

Give the output filename prefix. If not given, the output will be written to X-ligand.

Example:

$ pdbtop ligand -i 92v.pdb -o 92v-1

There will be several outputs:

• 92v-1.pdb: the ligand in PDB format.

• 92v-1.psf: the ligand topology in PSF format.

• 92v-1-naive.prm: the ligand parameters in CHARMM format.

However, you should check the ligand parameters carefully, as the generated force field parameters may NOT be reasonable, especially charges.

--pbc

Mandatory	No
Argument	6 or 9 real numbers.
Default	None

Give the periodic boundary condition. If not given, the ligand will be treated as a non-periodic system. The periodic boundary condition can be 6 or 9 real numbers:

$ pdbtop ligand -i pentancene.xyz --pbc "5. 5. 5. 90. 120. 90." # 6 numbers means "A B C alpha beta gamma"
$ pdbtop ligand -i pentancene.xyz --pbc "5.95900000 0.00000000 0.00000000 0.02651499 7.59595372 0.00000000 0.93662692 2.37133022 15.39997192" # 9 numbers means T1, T2, T3.

A good feature is that it can automatically adjust atoms to assemble fewest molecular fragments, making the ligand human-friendly.

--super-cells

Mandatory	No
Argument	3 integers.
Default	None

Give the number of cells in each dimension. The output molecule will be a supercell of the giant molecule.

$ pdbtop ligand -i pentancene.xyz --pbc "5. 5. 5. 90. 120. 90." --super-cells "2 2 2"

5.2. Theoretical Background

5.2.1. Atom Typing and RESP Charges

In *.psf, the atom types are guessed by a graph neural network, which is trained on CHARMM36 force field. The types are not guaranteed to be correct, and you should check them carefully. For example,

92v-1.psf

   39 !NATOM
    1 A      203    92V  C10  CG2R61   -0.115000       12.0096           0
    2 A      203    92V  C13  CG331    -0.370000       12.0096           0
    3 A      203    92V  C21  CG321    -0.280000       12.0096           0
    4 A      203    92V  C22  CG321    -0.280000       12.0096           0
    5 A      203    92V  C01  CG25C1   -0.100000       12.0096           0

The atom type for C10 is guessed to be CG2R61, and charge is \-0.115000.

In most cases, you should fit charges by yourself for a new ligand. A widely accepted way to compute charges is to use the RESP (restrained electrostatic potential)method, which is a two-step process. The first step is to compute the electrostatic potential (ESP) of the molecule using quantum mechanical calculations. The second step is to fit the charges to the ESP using a least-squares fitting procedure. Here, we recommend to use Qbics to do the quantum chemical calculation to obtain a wavefunction file (*.mwfn), then use Multiwfn with the *.mwfn file to calculate RESP charges. The practical way to compute RESP charges is shown Tutorial 2: Ligand Preparation.

Make sure that the sum of RESP charges of the ligand is equal to the total charge of the ligand.

5.2.2. Force Field Parameters

In *-naive.prm, the force field parameters are generated by searching for the most similar atom types in CHARMM36 force field. The parameters are not guaranteed to be reasonable, and you should check them carefully. For example,

92v-1-naive.prm

...
BONDS
CG2O1   NG2S1    370.00000000      1.34500000
CG2O1   OG2D1    620.00000000      1.23000000
CG2O6    FGA3    300.00000000      1.32359548 ! Guess
CG2O6    FGA3    300.00000000      1.32390861 ! Guess
CG2O6    FGA3    300.00000000      1.33970370 ! Guess
CG321    HGA2    309.00000000      1.11100000
CG321   CG321    222.50000000      1.53000000
CG321   CG323    300.00000000      1.48913599 ! Guess
...

The parameters with ! Guess are the ones that are guessed by pdbtop. You should check them carefully.