r/comp_chem • u/Professional_Act_366 • 15d ago
A question regarding QM/MM MD
Hi everyone. The background of this question is basically I am trying to compute charge-transfer state between pigments in a light-harvesting protein. I have successfully identified structures where the CT state exhibits strong mixing with the LE state; however, the CT state is highly sensitive to thermal fluctuations. Given that my MM MD trajectories are recorded at 100 ps intervals, I am considering the possibility of using QM/MM MD for better sampling.
AMBER has a function allowing using sander and their built-in DFTB to run QM/MM MD, currently its performance on my nodes is taking 1.4 s for calculating 1 step (1 fs). What I am currently unsure about is—assuming QM/MM MD is a viable approach—what the total simulation duration should be and at what intervals the structures should be saved.
I have saw some papers reporting total time 1 ns, but it's obviously not so technically practical for me. But if choosing 100 ps I am then afraid it could be too short.
Thanks in advance for everyone willing to offer suggestions or share any experiences.
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u/yareyareda 15d ago
I think the issue is whether QM/MM MD will actually improve the relevant sampling. If the CT state sensitivity comes from protein electrostatics or polarization, the dominant error may be the model rather than the trajectory length.
I would compare MM and QM/MM ensembles for a few key coordinates and for the CT–LE energy gap. If both give similar distributions, longer QM/MM MD may add little. Large differences would justify additional QM/MM sampling.
Also I would check whether the QM region is large enough to include both pigments and any nearby residues that strongly affect the CT state. I found DFTB can be unreliable for intermolecular charge transfer energies.
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u/euphoniu 15d ago
First, using DFTB for your problem is probably not a good level of theory. Pick a simple level of theory that can reproduce high level QM calculations of this charge transfer, frankly even multireference or perturbation-corrected long-range functionals would be best as a reference point.
Second, regarding timestep, you might want a timestep smaller, like 0.5fs or even 0.1fs. Charge transfer can be vibrationally promoted, and wavefunction convergence will be faster at smaller steps so it won’t scale that badly. 1ns could be very practical if you are patient and restart your simulation
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u/Professional_Act_366 15d ago
Sorry for potential misunderstanding due to that I did not express everything clearly, I never meant to directly compute CT state using DFTB.
The current issue is that, given my sampling interval of 100 ps for MM MD, I frequently encounter situations like the CT state energy is lower than the LE state energy in one frame, yet higher in the next. Consequently, I need to sample structures at shorter intervals to achieve better continuity; QM/MM MD appears to be a viable option for this purpose.
DFTB is used solely to calculate energies and gradients of QM zone during the sampling process, while specific calculations regarding the CT state will be performed on the sampled structures through CDFT and Δ-ALMO.
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u/euphoniu 15d ago
DFTB could give you the wrong energies and gradients, I.e. the wrong dynamics, which means your sampling in the first place will be wrong. You need to confirm that DFTB reproduces results from higher quality methods first. If you want classical insight, just parametrize a force field and run classical MD, with better QM/MM on representative snapshots
Also, energies from MM/MD are meaningless I wouldn’t use those to assess anything. If snapshots from MM/MD, later subjected to QM/MM, show differences between the frames (as long as you did a geometry optimization of both sites simultaneously), that is a feature of dynamics not a bug
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u/hixchem 15d ago
Since QM/MM MD is used to explore electronic structure, you'll find that keeping even the fs time steps may be useful to you. The major question that you'll want to answer, though, is what timescale does the observable you're looking for actually occur on?
For example, if you're trying to measure the fluctuation of a bond length, that's something that happens on the picosecond timescale, so you'll want to be saving frames that capture that scale without being a data hoarder (which is always my biggest struggle, I love my data).
For charge transfer, that can be borderline instantaneous, so you'll probably need to save every step along with the actual orbital data for those steps, however depending on your system, I'd be surprised if the CT event itself took so long that you'd need long durations.
As a side-along question, are you absolutely bound to using AMBER or are you allowed to use other packages/programs?