Is reference to bulk water energetics done automatically in CPPTRAJ GIST?

[noahharrison64]

Hi,
I'm using GIST to measure energetics of water displacement upon ligand binding to a protein cavity. I've been following this tutorial from ambermd.org. It is my understanding that to calculate the free energy difference of water transfer, I need to subtract the energy of water in bulk from the energy on the surface of the protein. This can be achieved by referencing the water-water term to bulk. I.e., for every voxel you can use Table 28.3 in the GIST manual to obtain water mean energies and densities for the water model you use. For my system, the energy is -9.533 and the density is 0.0329.

Eww (referenced enthalpy) = Eww + ((-9.533 (mean energy) * 0.0329 (number density)). * gO(Gist density)

Eww(referenced enthalpy) can then be used to calculate total enthalpy:

Etotal(referenced) = Esw + Eww(referenced enthalpy).

Am I correct in thinking that the tutorial does not include the reference to bulk water steps, and that this isn't automatically applied when running CPPTRAJ GIST?

Thanks,
Noah

[drroe]

Hi,

If I understand the questions correctly, the answer is yes, the bulk density is taken into account, but specifically for the data labeled 'norm' in the output (e.g. Esw-norm). Bulk density is specified by the refdens keyword and defaults to 0.0334 mols/Ang^3.

@fwaibl, @tkurtzman, and/or @EricChen521 may want to comment further.

[fwaibl]

Hi,

the bulk density is used to scale the oxygen and hydrogen densities, and also in the entropy calculation, basically to define the entropy of bulk water. But AFAIK it does not affect any of the energy columns, since Eww_dens is just the energy of all water molecules in that voxel and divided by the voxel volume, and Eww-norm is scaled by the average number of waters in that voxel.

It is correct that the bulk energy isn't automatically subtracted in cpptraj, and this must be done manually in post-processing. To reference Eww, you would compute
Eww_ref_norm = Eww_norm - (-9.533)
Eww_ref_dens = Eww_dens - (-9.533 * population / n_frames / voxel_volume)

If that is of any help, I have a small python package on https://github.com/liedllab/gisttools which automates those conversions.

Best regards,
Franz

[tkurtzman]

Hi, The energies are not referenced to bulk. Ideally when you perform your reference calculations to bulk, you should run a system of neat water using the same model of water (OPC, TIP4P-Ew, etc...), the same thermodynamic conditions, and the same MD engine. Use the neat water energy and densities obtained from these neat water simulations for use in your reference calculations. Tom

…

On Fri, Nov 18, 2022 at 3:56 PM Franz Waibl ***@***.***> wrote: Hi, the bulk density is used to scale the oxygen and hydrogen densities, and also in the entropy calculation, basically to define the entropy of bulk water. But AFAIK it does not affect any of the energy columns, since Eww_dens is just the energy of all water molecules in that voxel and divided by the voxel volume, and Eww-norm is scaled by the average number of waters in that voxel. It is correct that the bulk energy isn't automatically subtracted in cpptraj, and this must be done manually in post-processing. To reference Eww, you would compute Eww_ref_norm = Eww_norm - (-9.533) Eww_ref_dens = Eww_dens - (-9.533 * population / n_frames / voxel_volume) If that is of any help, I have a small python package on https://github.com/liedllab/gisttools which automates those conversions. Best regards, Franz — Reply to this email directly, view it on GitHub <#998 (comment)>, or unsubscribe <https://github.com/notifications/unsubscribe-auth/AGYKFQ3ZTQLVSUNSRLGW2HTWI7UPVANCNFSM6AAAAAASCOEJLQ> . You are receiving this because you were mentioned.Message ID: ***@***.***>

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