Preparing to run biomolecular QM/MM simulations with CP2K using AmberTools

AmberTools package has multiple tools to prepare, simulate and analyse biological systems.

You should familiarise yourself with tleap, pamred, nab, cpptraj, antechamber, parmch2 and sander as they will ususally be helpful to set up a biological system.

tleap is used to generate topologies and coordinates for biological molecules.

cpptraj is used to postprocess and analyse AMBER trajectories.

antechamber is used to create parameters for non-standard aminoacids and drug-like molecules.

sander runs molecular dynamics simulations

parmed allows modifying AMBER topologies

SSH to ARCHER

Load Ambertools with module load.

pdb4amber does a preliminary check on your PDB file and cleans potential errors in the protein structure.

ALWAYS assess the protonation state of your system at the pH of interest.

PROPKA and H++ server predict the protonation state of each aminoacid of protein.

openbabel is a chemical toolbox designed to search, convert, analyze, or store data from molecular modeling, chemistry, biochemistry, or related areas.

Generating parameters for non-conventinal residues is not easy and there are different ways to parameterise them.

The quality of the parameters is important to obtain valid results.

antechamber creates parameters for a non-conventional residues.

parmchk2 checks for missing parameters in the forcefield.

ALWAYS check the parameters for your system and test that they behave as expected.

LEap creates topologies and initial coordinates in AMBER format.

LEap can generate initial coordinates from scratch if needed.

xLEap (with GUI) and tLEap (through the terminal) are the two flavours of LEap.

Your MM system should always be neutral, add counterions to neutralise your system.

ALWAYS visualise and check the structures created by LEap.

After adding water molecules and combining coordinates of different system elements we have to minimise the system to fix any bad contacts (LEap had warned us already of some bad contacts in the structure).

Removing bad contacts at this point will prevent our system from failing catastrophically later down the line.

Combining different minimisation methods is a good practice and can help to avoid getting stuck into a local minima.

Thermalisation takes our system up to the target temperature.

Using a temperature ramp is a good way to slowly increase the system temperature and avoid your system from blowing up due to some bad contacts in your coordinates. You can set up a temperature ramp using the NMR restraint options of sander.

Density equilibration fixes the water density and corrects the size simulation box. It prevents air bubbles in our system that might cause simulation artefacts.

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 in cpptraj recenters the solute and fixes most of the PBC problems of the simulation.

Choosing the QM region is in not trivial.

You should also equilibrate the system using QM/MM ensemble before running your QM/MM production runs.

Instabilities between the QM and the MM regions are likely to show up in this monitorisation run.