Adding missing LJ parameters and recentering coordinates
Overview
Teaching: 10 min
Exercises: 0 minQuestions
Does the MM forcefield have all the parameters to run a QM/MM simulation?
How do I modify an Amber topology?
Objectives
Find missing parameters in the AMBER forcefields using
parmed
.Use
parmed
to change parameters in AMBER7 topologies.Use
cpptraj
to recenter the system in the simulation box.
Adding Lennard-Jones parameters using parmed
By construction, some hydrogen atoms do not have Lennard-Jones parameters in the AMBER forcefields. However, before running any QM/MM simulation, we need to provide those parameters. In particular, we are going to add the values of the hydrogen atom that correspond to the hydroxyl in the GAFF forcefield to TIP3P water model and to the hydroxyl groups from serine and tyrosine residues.
To do that, we will use the parmed
tool of the AmberTools package. The usage of this program is similar to LEap. First, we load the topology file in parmed
and then we do have a lot of options to modify it (More information here).
parmed system.parm7
We can check if there are missing parameter by printing an atom index (4685 corresponds to the hydrogen atom of the first water molecule) using the printDetails
command. Here we can see that the LJ Radius and LJ Depth values are set to 0.
printDetails @4686
The mask @4686 matches 1 atoms:
ATOM RES RESNAME NAME TYPE At.# LJ Radius LJ Depth Mass Charge GB Radius GB Screen
4686 776 WAT H1 HW 1 0.0000 0.0000 1.0080 0.4170 0.8000 0.8500
To modify them we need to use the changeLJSingleType
command on different atom types (:WAT@H1, :SER@HG and :TYR@HH).
changeLJSingleType :WAT@H1 0.3019 0.047
changeLJSingleType :WAT@H2 0.3019 0.047
changeLJSingleType :SER@HG 0.3019 0.047
changeLJSingleType :TYR@HH 0.3019 0.047
parmed
prints the following information everytime you change a LJ value.
It is very important to do this before running your QM/MM simulations. This step prevents creating unphysical interactions between the hydrogen atoms without LJ parameters and the QM subsystem. After this topology correction, the thermostat should stay stable during the QM/MM calculation.
Changing :WAT@H1 Lennard-Jones well depth from 0.0000 to 0.0470 (kal/mol) and radius from 0.0000 to 0.3019 (Angstroms)
Finally, we save a new topology using the command outparm
and exit.
outparm system_LJ_mod.parm7
quit
TIP
You can also run
parmed
with an parmed.in input file similarly as we did withtleap
.parmed system.parm7 -i parmed.in
Centering the solutes in the simulation box
Last but not least, we need to recenter the protein to the center of the simulation box using cpptraj
. cpptraj
is the trajectory analysis tool of the AmberTools package and it can do a lot of different analysis (you can find more information here). In this tutorial, we are only going to use it to recenter the system and make sure the coordinate file is in the correct format.
First, we need to load the topology file:
cpptraj -p system_LJ_mod.parm7
Then, we provide cpptraj
three different commands:
trajin
: input trajectories. It can be repeated as many times as trajectory file you want to analyse.trajout
: output trajectories specifying the desired format.autoimage
: recenters protein coordinates and fixes the simulation box around it.
After you have typed all your analysis commands you have to type go
or run
to actuallt make cpptraj run the analysis.
trajin system.equil.rst7
autoimage
trajout system.equil0.rst7 inpcrd
go
quit
Once we have the corrected topology and coordinates, we can start equilibration our QM/MM system. Before you go to the next step, make sure you have the following files:
system_LJ_mod.parm7
system.equil0.rst7
Key Points
In the MM forcefields, hydrogen atoms do not have Lennard-Jones parameters.
Adding missing Lennard-Jones parameters to the topology will prevent having unphysical interactions int the QM/MM boundary.
You can modify amber topologies using
parmed
.You should recenter the system to avoid having a split QM region in the QM/MM.
cpptraj
is the main analysis and postprocess trajectory tool for Amber.Using
autoimage
incpptraj
recenters the solute and fixes most of the PBC problems of the simulation.