Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method

A Enhanced QM/MM Method overcomes simple issues in normal QM/MM simulation. The Six QM/MM Method accelerates select assembly for the QM region, and can capture the chemical reaction pathways result in defining reaction coordinate. With this protocol, we successfully captured a chemical reaction pathways of double proton transfer and a reveal a deuterium substitution effect on a transfer mechanism of provency in water.

The protocol can be used to explore halogen or our deuterium substitution in heat identification in drug discovery. The main advantage of Six QM/MM Method is that, we don't need it to define brine reaction coordinate or introduce an device for chemical reaction pathway when exploring reaction mechanism. enable us to identify possible reaction pathways that in from react.

The method that can be used and extended to a high level QM Method and it could become a important tool to investigate the reaction mechanism for chemical reaction in solution. To begin this procedure, initiate the presets by setting runtype as 100, temp0 as 300, templow as 260, temphigh as 1300, and step as 120, 000 in the input file. Then, issue the appropriate command as shown here.

During the preset stage, monitor the energy of each term to calculate the mean values. Use the grep Linux commands to extract the energy. To modify the average energies in the md-input file, calculate the average energies based on the output of the previous command line, and to modify the v-shift line in the input file with the newly generated averages.

Initiate offsets in the QM4D program by typing the command to start the optimization step. Next, plug the energy propagation with the grace program, and make sure the energy fluctuation can cover the lowest and the highest ends of the temperature range. After optimization, save the final nk values of the offset step into a new file which is named nk.

dat in this protocol. To prepare the md-input file, set the runtype as one in the new input file to start the production simulations step. Specify the file name with the stored nk file as nkfile nk.

dat in the input file. The number of time steps was set as 6, 400, 000 in the present systems. The simulation counter is system dependent so change the simulation stat based on your specific demand.

Select a proper number of time step to use for marginal transition between different states for your own system. Initial the production in these simulation, by issuing the appropriate command to start MD Simulations. To monitor the bond forming and breaking process during the production phase, use the grep command to check the distance changes of H1N1 and H1N2 along the simulation time.

The same operation can be conducted for H2N3 and H2N4. Then, plug the distance propagation using the accumulated distance value during the production's simulations. Extract the reaction coordinates, and the energy terms from the production output file generated by QM4D by grep command.

Organize the data in four columns, and write them into the data file at each timeframe. Calculate the free energy by issuing the appropriate command. Finally, to project the free energy on the two-dimensional landscape, type the appropriate command.

The single deuterium substitution effect on double proton transfer process in porphycene was examined in the current protocol. The potential energy of the QM subsystem, and the water during the pre-equilibrium and optimization steps were checked to make sure the energy of the QM region had been broadened to a wider energy range, without effecting the energy of the environment. The representative distance and angle changes, and the projected free energy changes were used to characterize the deuterium substitution effect on the geometry and proton transfer process of porphycene.

The Six QM/MM Method achieves enhanced assembly in the energy space. The specified merger range should achieve broadened energy distribution. This method not only capture the top of reaction channel you got can transfer, but it also has a potential of identifying reaction products from norm reaction states result from reaction mechanism.

This protocol acts as a starting point to investigate the chemical reaction mechanisms in a condensed environment. Higher level QM methods can be readily combined with the Six QM/MM Method to explore more complex systems in the future.