(Note: These tutorials are meant to provide illustrative examples of how to use the AMBER software suite to carry out simulations that can be run on a simple workstation in a reasonable period of time. They do not necessarily provide the optimal choice of parameters or methods for the particular application area.)
Copyright Ross Walker 2015

A Simple Coupled Potential QM/MM Simulation

SECTION 1

A Coupled Potential QM/MM Simulation

By Ross Walker

Updated for AMBER 15

1) Setting up NMA

In this tutorial we will run two simulations and compare them. In the first simulation we will run a classical MD simulation of N-methylacetamide (NMA) in a periodic box of TIP3P water. In the second simulation we will run the same thing but this time we will use the semi-empirical PM3 Hamiltonian to calculate the energy and force on the NMA molecule.

The first stage is to build a topology and coordinate file for NMA in TIP3P water. NMA is simply an ACE and an NME residue joined together. As such it's structure is simple enough that we don't need to bother obtaining an initial pdb structure. We can simply create a "fake" pdb file and have xleap add all the missing atoms for us.

In this "fake" pdb file we simply specify the first atom of the two residues. Xleap will add the missing atoms for us. We give it a "semi" reasonable guess at the coordinates of the two atoms we specify just to make xleap's job a little easier:

ATOM     1   C   ACE     1       0.000   0.000   0.000
ATOM     2   N   NME     2       3.000   1.000  -1.000
TER

Let's load this into xleap so it can add the missing atoms.

$AMBERHOME/bin/xleap -s -f $AMBERHOME/dat/leap/cmd/leaprc.protein.ff14SB
NMA = loadpdb NMA_skeleton.pdb

xleap will not have added the missing atoms in ideal locations so we will use xleap's internal minimizer to improve the structure slightly:

edit NMA

Rubberband the whole structure to highlight it and then select Edit->Relax Selection

Ok, now we have a reasonable structure we can go ahead and add our solvent box. First close the unit editor (Unit->Close). First we need to load solvent parameters - for this tutorial we will use the TIP3P solvent model:

source leaprc.water.tip3p

Now we add a solvent box of 15 angstroms around the center of our NMA unit. For this we will use the Solvatebox command. To get help on this command type:

help solvatebox

As you can see the solvatebox command takes three mandatory arguments and one optional argument:

solvatebox solute solvent buffer [ "iso" ] [ closeness ]

In this case our solute is the NMA unit we created. For the solvent we will use TIP3PBOX. This is a pre-equilibrated box of TIP3P water. Type "edit TIP3PBOX" if you want to take a look at it. For buffer we will specify 15 which means we want a solvent box of 15 angstroms between any atom in our NMA and the edge of the box. This should be large enough for our purposes. So the command we run is:

solvatebox NMA TIP3PBOX 15

Xleap should report that it added 1522 residues. If we edit the NMA unit we should now see our solvent box.

edit NMA

Now we can go ahead and save our topology and coordinate files. There is no need to charge neutralize our system since our NMA unit is neutral.

saveamberparm NMA NMA.prmtop NMA.inpcrd

Here are the files: NMA.prmtop NMA.inpcrd