Compatibility with general small molecule forcefields

[kantundpeterpan]

Hello!

This is more of a question than an issue.

Let's say we want to simulate a protein-ligand complex. For the protein we use the Amber forcefield and for the ligand GAFF. However, the ligand is a little too "complicated" for the atomtypes parameterized in GAFF. So I wondered whether obtaining parameters with QuickFF (appropriate QM level of theory, fitting of the correct Amber style potentials, LJ parameters from GAFF) is a possibility here and whether these parameters can be considered compatible with the protein forcefield?

Thanks for any help

Greeting from France

[lvduyfhu]

Hello,

fitting a force field for the ligand is certainly possible if indeed an appropriate QM level is chosen for the training data. Whether or not the resulting force field is "compatible" with the GAFF force field for the protein is difficult to say in general. One always has to take care for combining different force fields. However, considering that QuickFF only fits the covalent intramolecular interactions, and that the ligand-protein interaction is goverend by non-bonding intermolecular interactions (i.e. electrostatic, van der Waals, ...) which is described by GAFF parameters for both ligand and protein, I would think that it is OK.

However, as I mentioned before, one always has to take care with combining force fields, and therefore I do not guarantee its validity/succes.

all the best,
Louis