PMX Ligand Preparation from Scratch - Atom Types and Parameter Discrepancies

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Dear All

We are writing to you regarding the preparation of ligands from scratch for running in PMX. We obtained the SDF file for the ligand from the following reference: [https://pubs.acs.org/doi/10.1021/ja512751q]

Our procedure was as follows:

  1. Hydrogen atoms were added to the SDF file.

  2. The file was converted to .mol2 format.

  3. Acpype was used to generate the ligand input parameter files: ffMOL.itp, mol_gmx.pdb, and MOL.itp. We used all available force fields within acpype: Amber, GAFF, and GAFF2.

  4. We examined the generated .itp files and encountered the following issues:

    1. The atom types in our generated ffMOL.itp and MOL.itp files do not match those in the PMX tutorial ligand files.
    2. The sigma and epsilon values in our .itp files differ significantly from those in the PMX tutorial files.

We are using the same ligand as in the PMX tutorials, extracted from the reference article. Our question is: how can we generate .itp files with the same atom type representation and sigma/epsilon values as the PMX tutorials, using acpype or any other suitable tool?

For your review and guidance, we have pasted the ffMOL.itp file from the tutorial and the generated 18625-1- ffMOL.itp file (corresponding to the 18625-1 molecule) by us. We would greatly appreciate your assistance in determining the next steps.

Thank you for your time and help.

Thanks and regards

Jinuraj

ffMOL is shown below (From the pmx tutorial)
[ atomtypes ]
c 0.000000 0.000000 A 0.331521 0.413379
ns 0.000000 0.000000 A 0.326995 0.491202
cl 0.000000 0.000000 A 0.346595 1.103740
ca 0.000000 0.000000 A 0.331521 0.413379
h1 0.000000 0.000000 A 0.242200 0.087027
cg 0.000000 0.000000 A 0.347896 0.667766
o 0.000000 0.000000 A 0.304812 0.612119
DU 0.000000 0.000000 A 0.000000 0.000000
hn 0.000000 0.000000 A 0.110650 0.041840
n1 0.000000 0.000000 A 0.327352 0.459403
c3 0.000000 0.000000 A 0.339771 0.451035
hc 0.000000 0.000000 A 0.260018 0.087027
ha 0.000000 0.000000 A 0.262548 0.067362
os 0.000000 0.000000 A 0.315610 0.303758
nb 0.000000 0.000000 A 0.338417 0.393714
nv 0.000000 0.000000 A 0.336813 0.468608

18625-1_ffMOL is given below(Generated by acpype)
[ atomtypes ]
CT 0.000000 0.000000 A 0.339967 0.457730
OS 0.000000 0.000000 A 0.300001 0.711280
CA 0.000000 0.000000 A 0.339967 0.359824
NC 0.000000 0.000000 A 0.325000 0.711280
N2 0.000000 0.000000 A 0.325000 0.711280
CM 0.000000 0.000000 A 0.339967 0.359824
CZ 0.000000 0.000000 A 0.339967 0.359824
N1 0.000000 0.000000 A 0.325000 0.711280
C 0.000000 0.000000 A 0.339967 0.359824
O 0.000000 0.000000 A 0.295992 0.878640
Cl 0.000000 0.000000 A 0.347094 1.108760
HC 0.000000 0.000000 A 0.264953 0.065689
H1 0.000000 0.000000 A 0.247135 0.065689
HA 0.000000 0.000000 A 0.259964 0.062760
H 0.000000 0.000000 A 0.106908 0.065689

2

Ligand parameters in the tutorial were generated with acpype and gaff 2.1

The atom types that you pasted don’t seem to be from gaff, as they are in upper case. Could these be amber params?

Vytas