Proton Transfer between methylthiolate and phenol in a box of water

Files for this tutorial:


The protonation state of the active site cysteine residue of glutathione and its interacting partner Tyrosine-7 in Glutathione S-Transferases have been the subject of interest both by experimental and theoretical methods. Here we will examine the free energy profile for the transfer between analogues of these two residues (methythiolate and phenol molecules) in a box of water. The molecules involved in proton transfer will be represented by the QM potential, PDDG/PM3, while the water molecules will be represented through a molecular mechanics force field. The inputs show how to use DYNAMO to perform umbrella sampling molecular dynamics simulations. The data files are then used to construct a free energy profile. Please note: A real research application would do longer sampling in each window and the window spacing would be more fine-grained.

1. The full constructed system is given as cystyr-solv.sys_bin (the binary describing the system) and cystyr-solv.pdb. To construct these systems we needed to construct a force field for methylthiolate and phenol. But since these molecules are to be represented by QM mechanics then the terms for bond-stretching, bond-bending, dihedral rotation and charges could be set to zero. The Lennard-Jones terms still need to be assigned and were done by analogy to the charged state of cysteine and tyrosine residues.

2. The input to do a simple QM/MM minimization is given in:


To compile the program, do the following on jonas:

f90 -I$MOD_DIR -module $MOD_DIR -o cystyr-solv-min -O cystyr-solv-min.f90 $LIBRARY

You can then submit the job to the que:

qsub –q training

3. The input to do an umbrella sampling molecular dynamics simulation is given in


Note: You must first compile this program linking it to the MPI library to get a parallel executable.

$ f90 -I$MOD_DIR -module $MOD_DIR -o cystyr-solv-ussim -O cystyr-solv-ussim.f90 $LIBRARY -lmpi
qsub –q training

The output produced trajectory files, the final structure in PDB format and data collected on reaction coordinate values produced during the simulation for each window. It is this data that can be used to construct a free energy profile using the Weighted Histogram Analysis Method (WHAM).

To construct the free energy profile,

$ dynamo rxn1-wham