Step 2: QM and MM energies

We are going to start by using a simple python script to calculate the MM and QM/MM interaction energy between each side-chain and the water molecules in its waterbox. The script is called “energy.py” and you should find it in the current directory (the qmmm) directory). If you are curious, you can take a look at this script.

This script uses Sire to calculate both the MM energy using the Amber GAFF forcefield. It also uses the sqm program to calculate the QM/MM energy using one of five different semi-empirical Hamiltonians, which you can choose;

(1)AM1 : Austin Model 1, selected using the string “AM1”
(2)AM1/d : Austin Model 1 with dispersion corrections, selected using the string “AM1/d”
(3)PM3: Parameterized Model number 3, selected using the string “PM3”
(4)PM6: Parameterized Model number 6, selected using the string “PM6”
(5)DFTB: Density Functional based Tight Binding, selected using the string “DFTB”

The script calculates the electrostatic interaction energy between the side-chain and the water molecules in the water box using both MM and the chosen QM method. To use the script, type;

The script will print the QM/MM energy, the MM energy, and the difference between the two.

EXERCISE 1 - Compare the QM/MM and MM energies of the side-chains

Calculate the MM and QM/MM energies of both side-chains for each of the five semi-empirical Hamiltonians. Place these, together with the difference between the QM/MM and MM energies, into a table.

QUESTION 1.1 - Which side-chain has the strongest interaction with water? Does this make chemical sense?

QUESTION 1.2 - Which semi-empirical QM/MM model gives the strongest interaction between the side-chains and water? How does this compare to the interaction energies using MM?

If you get stuck or need help, you can take a peek at this model answer for exercise 1.

where “SIDECHAIN” is the name of the side-chain (“PHE” for phenylalanine and “TRP” for tryptophan) and “METHOD” is one of the five above semi-empirical methods (“AM1”, “AM1/d”, “PM3”, “PM6” or “DFTB”). For example, to calculate the MM and PM3 energies of tryptophan, you should type;