Studying Excited State Dynamics in Different pH Environments

[lukhman9020]

Dear Sir,

I hope this message finds you well. I am planning to study the excited state dynamics of a system in three different pH environments. For this, I was thinking of preparing the initial sampling using the AMBER CpHMD (Constant pH Molecular Dynamics) method.
For the excited state dynamics study, I am considering running QM/MM simulations with SHARC, MOLCAS, and TINKER, using the SA-CASSCF (State-averaged Complete Active Space Self-Consistent Field) method for the quantum mechanical part of the calculations.
I would like to know if this approach is correct or if there is anything else I should consider to properly account for the pH differences during the excited state calculations.
Looking forward to hearing from you.

Best regards,
Lukhmanul Hakeem K

[maisebastian]

Dear Lukhmanul,
sounds like an interesting project, but with a lot of challenges.
We have never done such simulations in our group, so we do not have any relevant experience. I would assume that what you propose makes sense, to have ground-state samples from the correct grand canonical ensemble (constant pH) and use them as initial conditions. If the excited-state simulations are not very long, then one could assume that within this short time the protonation state does not change dramatically, so that one could run the SHARC simulations without explicit constant pH algorithm. I would expect that this works better the bigger your solvent droplet is (because the exchange of protons with the environment happens there and a larger shell will make it take longer to affect the molecule). Also keep in mind that even with a big droplet, protons could jump anywhere within your droplet at any time (time constant is about 1ps 10.1021/acscentsci.9b00603). These proton jumps cannot be described currently with SHARC QM/MM, because normal force fields have fixed water molecules.

Best,
Sebastian

[lukhman9020]

Dear Lukhmanul, sounds like an interesting project, but with a lot of challenges. We have never done such simulations in our group, so we do not have any relevant experience. I would assume that what you propose makes sense, to have ground-state samples from the correct grand canonical ensemble (constant pH) and use them as initial conditions. If the excited-state simulations are not very long, then one could assume that within this short time the protonation state does not change dramatically, so that one could run the SHARC simulations without explicit constant pH algorithm. I would expect that this works better the bigger your solvent droplet is (because the exchange of protons with the environment happens there and a larger shell will make it take longer to affect the molecule). Also keep in mind that even with a big droplet, protons could jump anywhere within your droplet at any time (time constant is about 1ps 10.1021/acscentsci.9b00603). These proton jumps cannot be described currently with SHARC QM/MM, because normal force fields have fixed water molecules.

Best, Sebastian

Dear Sir,
Thank you for your prompt response to my previous queries. From our experimental data, we have thought that intermolecular proton transfer (molecule to solvent) occurs at different pH levels. I have a question, if we include water molecules with our molecule in the QM region of a QM/MM simulation, could we observe the proton transfer process directly?

Additionally, I recently came across a thesis from your group titled "Excited State Dynamics of 5,6-Dihydroxyindole, a Eumelanin Building Block in Water and Methanol." I noticed an image describing proton transfer between DHI and the solvent, which was adapted from a paper from your group titled "Sequential Proton-Coupled Electron Transfer Mediates Excited-State Deactivation of a Eumelanin Building Block." I believe this approach may offer a solution to my research problem.

If possible, could you kindly share a copy of the thesis to read more about this approach?

Thank you once again for your guidance and support.

Best regards,
Lukhmanul Hakeem K

[maisebastian]

Dear user,
indeed, if you have proton transfer between water and solute, then it is important to have water molecules in the QM region. Be aware that we did not do something like that in SHARC before. Depending on your initial conditions, it might be that different waters are near the molecule in each initcond, so you might need to reorder the waters appropriately, so that, e.g., the first 5 waters are the ones near the molecule. A simpler, but more approximate way would be to run the SHARC simulations with only a few waters, and have no MM region.

The thesis you mentioned is publicly available from the univie archive: https://utheses.univie.ac.at/detail/42935#

Best,
Sebastian

[lukhman9020]

Dear user, indeed, if you have proton transfer between water and solute, then it is important to have water molecules in the QM region. Be aware that we did not do something like that in SHARC before. Depending on your initial conditions, it might be that different waters are near the molecule in each initcond, so you might need to reorder the waters appropriately, so that, e.g., the first 5 waters are the ones near the molecule. A simpler, but more approximate way would be to run the SHARC simulations with only a few waters, and have no MM region.

The thesis you mentioned is publicly available from the univie archive: https://utheses.univie.ac.at/detail/42935#

Best, Sebastian

Dear Sir,
Thank you for your reply.

Best regards,
Lukhmanul Hakeem K

[lukhman9020]

Dear user, indeed, if you have proton transfer between water and solute, then it is important to have water molecules in the QM region. Be aware that we did not do something like that in SHARC before. Depending on your initial conditions, it might be that different waters are near the molecule in each initcond, so you might need to reorder the waters appropriately, so that, e.g., the first 5 waters are the ones near the molecule. A simpler, but more approximate way would be to run the SHARC simulations with only a few waters, and have no MM region.

The thesis you mentioned is publicly available from the univie archive: https://utheses.univie.ac.at/detail/42935#

Best, Sebastian

Dear Sir,

I am currently sampling 90 initial conditions using the AMBER interface and focusing on QM simulations (SHARC-MOLCAS) to study proton transfer between water and my molecule. I would like to clarify the following:

Is the MOLCAS quantum chemistry interface sufficient for these calculations, or is there any additional requirement to use TINKER or provide a force field for the system?

Looking forward to hearing from you.

Best regards,
Lukhmanul Hakeem K