In this practical you will compare molecular mechanics (MM) representations of the methylated side-chains of phenylalanine (PHE) and tryptophan (TRP) with quantum mechanics (QM) representations. Specifically, you will calculate the QM/MM relative hydration free energy of the side-chains and will compare it with the MM value. To do this, you will use QM/MM Monte Carlo to calculate the difference between a QM and MM representation of these side-chains, and will work out a free energy cycle that can use these differences to convert the MM relative hydration free energy into the QM/MM relative hydration free energy.

The practical will lead you through all of the theory needed to perform these calculations. You will use simple python scripts to build up and understand all of the parts of the calculation, before then using the quantomm program in Sire to calculate the result. Finally, you will compare the calculated values to experiment and see if modelling the side-chains using QM has improved the result.