QM/MM tutorial


QM/MM calculations on thymine dimer repair.


III. Setting up the system for QM/MM simulation

QM/MM subdivision

We will now set up the system for a QM/MM simulation with Gromacs. The dimerized thymine bases will be described at the semi-empirical AM1 level of theory, while the remainder of the system is modeled with the Amber99 forcefield. Figure 3 shows how we split up our system in a QM and MM part.

Figure 3. Division of the system in a QM subsystem and an MM subsystem. The QM subsystem is described at the semi-empirical QM level, while the remainder of the system, consisting of the reactants-aliphatic tail is modeled with the Amber99 forcefield. Link atoms are introduced at the QM/MM boundary to cap the QM subsystem.

The QM/MM division splits the systems along a chemical bond. Therefore, we need to cap the QM subsystem with a so-called link atom (la, figure 4). This link atom is present as a hydrogen atom in the QM calculation step. It is not physically present in the MM subsystem, but the forces on it, that are computed in the QM step, are distributed over the two atoms of the bond. The bondlength itself is constrained during the computations.

To make use of the QM/MM functionality in Gromacs, we have to

Adding Link Atoms

At the bond that connects the QM and MM subsystems we introduce a link atom. In Gromacs we make use of a special atomtype, called LA. This atomtype is treated as a hydrogen atom in the QM calculation, and as a dummy atom in the forcefield calculation. The link atoms, if any, are part of the system, but have no interaction with any other atom, except that the QM force working on it is distributed over the two atoms of the bond. In the topology the link atom (LA), therefore, is defined as a dummy atom:

[ dummies2 ]
LA QMatom MMatom 1 0.73
Note, a link atom has no mass.
Furthermore, the bond between the MM and QM atoms is maintained at the forcefield level:
[ bonds ]
QMatom MMatom 1
Note that, because in our system the QM/MM bond is a carbon-nitrogen bond (0.153 nm), we use a constraint length of 0.153 nm, and dummy position of 0.65. The latter is the ratio between the ideal C-H bondlength and the ideal C-C bond length. With this ratio, the link atom is always 0.1 nm away from the QMatom, consistent with the carbon-hydrogen bondlength. If the QM and MM subsystems are connected by a different kind of bond, a different constraint and a different dummy position, appropriate for that bond type, are required. Note that because the link atoms are constructed at each step of the simulation, it is not relevant a what position the link atoms are introduced in the configuration file. Thus, we can simply place the two linkatoms at the origin (0,0,0). Click to have a look at what the
structure and topology files should look like for a QM/MM simulation.

Specifying the QM Atoms

Once we have decided which atoms should be treated by a QM method, we add these atoms, including the link atoms, if any, to the index file. We can either use the make_ndx program, or hack the atoms into the index.ndx file ourselves. The index file we will use in this tutorial is found here: qmmm.ndx. It is possible to constrain the bonds in the QM subsystem along. It is also possible not to constrain them, while the bonds in the MM subsystem are. This is essential for instance if the QM atoms are supposed to undergo bond-breaking/formation reactions. In this case, Gromacs' bondtype 5 is used for the bonds in the QM subsystem:

[ bonds ]
QMatom1 QMatom2 5
QMatom2 QMatom3 5

Specifying the QM/MM Simulation Parameters

The last thing we need to do to setup gromacs for performing QM/MM calculations is to specify what level of QM theory gromacs has to use for the QM subsystem, what QM/MM interface to use, what multiplicity the QM subsystem has, and so on. All these things are defined in the mdp file. The following option lines need to be included for a QM/MM run:

QMMM = yes
QMMM-grps = QMatoms
QMmethod = RHF
QMbasis = STO-3G
QMMMscheme = ONIOM
QMcharge = 0
QMmult = 1
Note that the default options are shown here. The actual options depend on the system. The mdp file we will use for the short QM/MM equilibrtion simulation is located here: qmmm1.mdp. In case one choses as the QMmethod a semi-empirical method, such as AM1 or PM3, the QMbasis is ignored.

Finally, the default amber distributions for gromacs do not include link atoms yet. Thus, we need to add them by hand. At the end of the ffamber99.atp file, we include:

LA 0.0; Link Atom for QM/MM
This allows pdb2gmx to recognize the link atoms if they are present in your input structures. We also add the link atom to the ffamber99nb.atp file:
LA LA 1 0.0000 0.0000 A 0.0 0.0
This line allows grompp to understand what Lennard-Jones parameters to use for the link atom, which are zero for obvious reasons. The integer is the element type to be used in QM/MM calculations. The link atom is considered a hydrogen (1).

With this setup, we will perform a short 1ps QM/MM MD simulation.

Next:IV. Performing a QM/MM simulation of the system
Previous: II. Equilibration of the DNA

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updated 28/10/08