Thanks, Stephan and Patricio for the helpful discussion here!
Joe
------
Joseph Baker, PhD
Barbara Meyers Pelson Chair in Faculty-Student Engagement (AY 2024-2027)
Professor, Department of Chemistry
The College of New Jersey
Ewing, NJ 08628
Chair-elect (2026), Trenton Local Section of the ACS
Chemistry Division Representative (2024-2027), The Council on Undergraduate
Research
On Wed, Jun 17, 2026 at 11:55 AM Stephan Schott via AMBER <amber.ambermd.org>
wrote:
> Hi,
>
> I was just made aware of this discussion. While packing "big" systems,
> Nikolai Skrynnikov et. al, Dan Roe and myself found that the truncated
> octahedron used by LEaP would result in the solvated object to protrude
> from the PBC, making clear that the way the truncate octahedron was been
> calculated until the last release was wrong, but the error is not obvious
> for small/globular systems. The explanation from Patricio is spot on: the
> diagonal distance was not being respected, making all systems be closer to
> the boundary than desired. The bugfix results in the behavior you are
> seeing, which should actually make the distance be 14 from the solute to
> the boundary. I am afraid a proper comment in the manual regarding this fix
> is missing, so I will add something as soon as I can.
>
> Long story short, solvateOct will result in bigger systems in Amber 2026
> onwards, and the new sizes are safer than the ones made until 2025,
> actually respecting the padding distance entered by the user.
>
> Best regards,
>
> Stephan Schott Verdugo
> Biochemist
>
>
> Computational Biophysical Chemistry
> Institut für Bio- und Geowissenschaften / Bioinformatik (IBG-4)
> Forschungszentrum Jülich GmbH
> Wilhelm-Johnen-Straße, 52425 Jülich
> Germany
>
>
> ---------------------------------------------------------------------------------------------
>
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>
> El mié, 17 jun 2026 a la(s) 3:03 p.m., Baker, Joseph via AMBER (
> amber.ambermd.org<mailto:amber.ambermd.org>) escribió:
> Hi Patricio,
>
> Thanks for the detailed response here! Yes this makes sense. Using the
> older solvation routine seemed fine for us for this particular system (we
> monitor for self-interactions in our trajectories routinely to catch that
> type of thing). But it sounds like the fixed approach to solvateoct will be
> better at preventing some edge cases going forward and is a safer bet
> against self interactions (assuming of course that the protein doesn't
> wildly unfold/display dramatic conformational changes during the
> simulation)?
>
> Joe
>
>
> ------
> Joseph Baker, PhD
> Barbara Meyers Pelson Chair in Faculty-Student Engagement (AY 2024-2027)
> Professor, Department of Chemistry
> The College of New Jersey
> Ewing, NJ 08628
> Chair-elect (2026), Trenton Local Section of the ACS
> Chemistry Division Representative (2024-2027), The Council on Undergraduate
> Research
>
>
> On Tue, Jun 16, 2026, 7:25 PM Patricio Barletta via AMBER <
> amber.ambermd.org<mailto:amber.ambermd.org>>
> wrote:
>
> > Oh, ok, it's the calculation of the bounding box necessary for the atom
> > centers (given the buffer length you selected), what changed:
> >
> > Before:
> > ```
> >
> > Scaling up box by a factor of 1.464352 to meet diagonal cut criterion
> >
> > Solute vdw bounding box: 137.890 98.975 70.390
> >
> > Total bounding box for atom centers: 178.892 178.892 178.892
> >
> > ...
> > RESULTING BOX SIZE: 155.7907688 155.7907688 155.7907688 109.4712190
> > 109.4712190 109.4712190
> > ```
> >
> > After*:
> > ```
> >
> > Scaling up box by a factor of 1.260286 to meet diagonal cut criterion
> >
> > Solute vdw bounding box: 137.890 98.975 70.390
> >
> > Total bounding box for atom centers: 209.069 209.069 209.069
> >
> > ...
> > RESULTING BOX SIZE: 181.9246991 181.9246991 181.9246991 109.4712190
> > 109.4712190 109.4712190
> > ```
> >
> > So, you are right: there was a change in how the code calculates the box
> > size to guarantee the buffer length in the output, and it was an actual
> > bugfix. If you open both structures, you should see that along some
> > diagonal (normal to 2 of the octahedron faces), the solute atoms won't
> have
> > much water around them, and that they could be interacting with their
> > self-images.
> >
> > Here's my explanation of the fix, which I didn't do, so I appreciate any
> > corrections.
> >
> > What solvateoct does is first center the solute (your protein), and then
> > rotate it to align its principal axis along the XYZ axii. Then it takes
> the
> > solute bounding box (rectangular) and adds 2*buffer length to the longest
> > axis to obtain the dimension of the initial cubic solvent box, from which
> > the corners are cut to form the truncated octahedron box.
> > The issue is that while this method guarantees your buffer length for a
> > cubic solvent box, it does not guarantee it for the truncated octahedron
> > that will be generated by the subsequent corner cutting. Some atoms will
> be
> > too close to the diagonal faces.
> >
> > So, solvateoct calls `ToolOctBoxCheck()`, which calculates a scaling
> > factor that ensures the initial cubic solvent box is large enough to
> > maintain the correct buffer length between the atom that pokes the most
> and
> > its closest octahedral face.
> >
> > The problem was that `ToolOctBoxCheck()` was scaling the buffer length
> > instead of the correct value. You can see it in the numbers you reported:
> >
> > ```
> > Length of largest axis for the initial solute vdw bounding box: 137.89
> > Buffer: 14 (on each side, so it's 2Xed)
> > Reported scaling factor: 1.464352
> > Length of cubic solvent box: 137.89 + 1.464352 * 2 * 14 = 178.892
> > ```
> > 178.892A was the dimension of your initial cubic solvent box. The length
> > of your final box size is 155.7907688A. That's because after all of this,
> > solvateoct calls `EwaldRotate()` and rotates all atoms. After that
> > rotation, the truncated octahedron gets mapped to a rhombohedron, which
> is
> > the convention pmemd uses.
> >
> > The problem with this procedure is that it assumes the depth it cuts is
> > determined solely by the buffer length (14A in this case), which you can
> > imagine would be problematic as the boxes get bigger.
> > If it worked like that, given a sufficiently large box, the truncated
> > octahedron would be almost the same as the original cubic solvent box.
> > BTW, the corner-cutting function is not affected by all of this and will
> > work correctly for the given cubic solvent box. The problem is that the
> > resulting distance between the atom and the diagonal face will be too
> close.
> >
> > Back to the numbers. The point at which corners are cut off depends on
> the
> > total cubic solvent box size. The initial cubic solvent box size is:
> > ```
> > 28A+137.890 = 165.89A
> > ```
> > This is the length of the cube edge, and this is the number that should
> > get scaled.
> > Since the solute bounding box is fixed and dwarfs the buffer (68.945A vs
> > 14A), scaling the buffer barely moves the half-box; so the diagonal face
> > distance falls short of the needed growth. The bigger the solute, the
> > larger the difference between these 2 methods will be.
> >
> > So, using the reported scaling factor we get that the new edge length is:
> > ```
> > 165.89A * 1.260286 = 209.069
> > ```
> >
> > Which is the edge length for the "Total bounding box for atom centers"
> you
> > are getting with the latest ambertools. After that, EwaldRotate does its
> > thing, and the final box length you get is `181.9246991A`.
> >
> > So, yes, it changed, but for the better. And while some of your MDs will
> > get slower, in this particular case you shouldn't have to pay such a big
> > price for the biggers solvent box. You have a very elongated protein. A
> > rectangular box might be a better fit.
> >
> > Best,
> >
> > *: "Total bounding box for atom centers" is misleading; it should say
> > "Total bounding box for atom spheres" or something like that, since the
> vdw
> > radii of the atoms are considered when building the initial cubic solvent
> > box.
> >
> > ________________________________
> > From: Baker, Joseph <bakerj.tcnj.edu<mailto:bakerj.tcnj.edu>>
> > Sent: Tuesday, June 16, 2026 4:26 PM
> > To: Patricio Barletta <pb777.iqb.rutgers.edu<mailto:
> pb777.iqb.rutgers.edu>>; AMBER Mailing List <
> > amber.ambermd.org<mailto:amber.ambermd.org>>
> > Subject: Re: [AMBER] solvateoct behavior in Amber26
> >
> > As for the density question, the initial densities, as you can see from
> > the tleap output, are not that far off from one another, so tleap is
> > getting the initial densities just fine, it is just adding a lot more
> water
> > in amber26.
> >
> > ------
> > Joseph Baker, PhD
> > Barbara Meyers Pelson Chair in Faculty-Student Engagement (AY 2024-2027)
> > Professor, Department of Chemistry
> > The College of New Jersey
> > Ewing, NJ 08628
> > Office: C212 Science Complex
> > Phone: (609) 771-3173
> > Web: www.bakercompchemlab.com<http://www.bakercompchemlab.com><
> http://www.bakercompchemlab.com/>
> > Social Media: Instagram<https://www.instagram.com/bakerlabtcnj/>,
> > LinkedIn<https://www.linkedin.com/in/joseph-baker-6b444758/>
> > Pronouns: he/him/his
> >
> > Chair-elect (2026), Trenton Local Section of the ACS
> > Chemistry Division Representative (2024-2027), The Council on
> > Undergraduate Research
> >
> >
> >
> > On Tue, Jun 16, 2026 at 4:07 PM Baker, Joseph <bakerj.tcnj.edu<mailto:
> bakerj.tcnj.edu><mailto:
> > bakerj.tcnj.edu<mailto:bakerj.tcnj.edu>>> wrote:
> > Hi Patricio,
> >
> > Very standard script, pasted at the bottom below. So we haven't been
> using
> > the iso/aniso options. As you can see we are using the ff19SB and OPC
> water
> > combo. As I mentioned, this same script run through multiple versions of
> > amber only starts adding a large number of extra waters when we hit the
> > amber26 version. As you can see the AmberTools25 and AmberTools23
> versions
> > of tleap both give a smaller number of OPC water residues added, and the
> > bottom of the rst7 file for each of these agree identically. It is only
> in
> > AmberTools26 where things start to change. Thanks for your help looking
> > into this! - Joe
> >
> > For example when I use AmberTools26 it gives me:
> >
> >
> > Loading PDB file: ../../00-structure/fold_full_sequence_model_0.pdb
> >
> > total atoms in file: 5271
> >
> > Leap added 4881 missing atoms according to residue templates:
> >
> > 4881 H / lone pairs
> >
> > Scaling up box by a factor of 1.260286 to meet diagonal cut criterion
> >
> > Solute vdw bounding box: 137.890 98.975 70.390
> >
> > Total bounding box for atom centers: 209.069 209.069 209.069
> >
> > (box expansion for 'iso' is 81.5%)
> >
> > Solvent unit box: 18.865 18.478 19.006
> >
> > Volume: 4635036.174 A^3 (oct)
> >
> > Total mass 2620962.702 amu, Density 0.939 g/cc
> >
> > Added 141329 residues.
> >
> >
> > and then the bottom of the rst7 is: 181.9246991 181.9246991 181.9246991
> > 109.4712190 109.4712190 109.4712190
> >
> > For example when I use AmberTools25 it gives me:
> >
> >
> > Loading PDB file: ../../00-structure/fold_full_sequence_model_0.pdb
> >
> > total atoms in file: 5271
> >
> > Leap added 4881 missing atoms according to residue templates:
> >
> > 4881 H / lone pairs
> >
> > Scaling up box by a factor of 1.464352 to meet diagonal cut criterion
> >
> > Solute vdw bounding box: 137.890 98.975 70.390
> >
> > Total bounding box for atom centers: 178.892 178.892 178.892
> >
> > (box expansion for 'iso' is 105.2%)
> >
> > Solvent unit box: 18.865 18.478 19.006
> >
> > Volume: 2910739.196 A^3 (oct)
> >
> > Total mass 1628046.894 amu, Density 0.929 g/cc
> >
> > Added 86216 residues.
> >
> > and then the bottom of the rst7 is: 155.7907688 155.7907688 155.7907688
> > 109.4712190 109.4712190 109.4712190
> >
> >
> > For example when I use AmberTools23 it gives me:
> >
> >
> > Loading PDB file: ../../00-structure/fold_full_sequence_model_0.pdb
> >
> > total atoms in file: 5271
> >
> > Leap added 4881 missing atoms according to residue templates:
> >
> > 4881 H / lone pairs
> >
> > Scaling up box by a factor of 1.464352 to meet diagonal cut criterion
> >
> > Solute vdw bounding box: 137.890 98.975 70.390
> >
> > Total bounding box for atom centers: 178.892 178.892 178.892
> >
> > (box expansion for 'iso' is 105.2%)
> >
> > Solvent unit box: 18.865 18.478 19.006
> >
> > Volume: 2910739.196 A^3 (oct)
> >
> > Total mass 1628046.894 amu, Density 0.929 g/cc
> >
> > Added 86216 residues.
> >
> >
> > and then the bottom of the rst7 is: 155.7907688 155.7907688
> 155.7907688
> > 109.4712190 109.4712190 109.4712190
> >
> > ----SCRIPT----
> >
> > #Load in the necessary forcefields
> >
> > source leaprc.protein.ff19SB
> >
> > source leaprc.water.opc
> >
> >
> > #Load the PDBs
> >
> > prot = loadpdb ../00-structure/fold_full_sequence_model_0.pdb
> >
> >
> > #solvate system
> >
> > solvateoct prot OPCBOX 14
> >
> >
> > #Adding Ions
> >
> > addIonsRand prot Na+ 0
> >
> > addIonsRand prot Cl- 0
> >
> >
> > #save files
> >
> > saveAmberParm prot sys.parm7 sys.rst7
> >
> >
> > # Quit
> >
> > quit
> >
> > ------
> > Joseph Baker, PhD
> > Barbara Meyers Pelson Chair in Faculty-Student Engagement (AY 2024-2027)
> > Professor, Department of Chemistry
> > The College of New Jersey
> > Ewing, NJ 08628
> > Chair-elect (2026), Trenton Local Section of the ACS
> > Chemistry Division Representative (2024-2027), The Council on
> > Undergraduate Research
> >
> >
> >
> > On Tue, Jun 16, 2026 at 3:46 PM Patricio Barletta via AMBER <
> > amber.ambermd.org<mailto:amber.ambermd.org><mailto:amber.ambermd.org
> <mailto:amber.ambermd.org>>> wrote:
> > *
> > Can I see the tleap script you are running? I'm curious about the water
> > model.
> > *
> > If you do tail -n1 <OUTPUT RST7 FILE> , do you get the same box size in
> > all cases?
> > *
> > If you run NVT on the output systems, do you get the same starting
> density?
> >
> > The coordinates for the pre-equilibrated water molecules are at
> > `amber/dat/leap/lib/`, and I don't see any change on files like
> > 'tip3pbox.off'.
> > The other factor that may affect the final result is the usage of the
> > keyword "aniso", that prevents tleap from centering and reorienting the
> > solute before adding the box. This increases the box size for a given
> > buffer length.
> >
> > Best,
> >
> > ________________________________
> > From: amber-request.ambermd.org<mailto:amber-request.ambermd.org
> ><mailto:amber-request.ambermd.org<mailto:amber-request.ambermd.org>> <
> > amber-request.ambermd.org<mailto:amber-request.ambermd.org><mailto:
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> <mailto:amber.ambermd.org>> <amber.ambermd.org<mailto:amber.ambermd.org
> ><mailto:
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> > Subject: AMBER Digest, Vol 4976, Issue 1
> >
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> > 1. solvateoct behavior in Amber26 (Baker, Joseph)
> >
> >
> > ----------------------------------------------------------------------
> >
> > Message: 1
> > Date: Tue, 16 Jun 2026 14:55:03 -0400
> > From: "Baker, Joseph" <bakerj.tcnj.edu<mailto:bakerj.tcnj.edu><mailto:
> bakerj.tcnj.edu<mailto:bakerj.tcnj.edu>>>
> > To: AMBER Mailing List <amber.ambermd.org<mailto:amber.ambermd.org
> ><mailto:amber.ambermd.org<mailto:amber.ambermd.org>>>
> > Subject: [AMBER] solvateoct behavior in Amber26
> > Message-ID:
> > <
> > CAA5VDpDSCstP8vGa_cQ3Nj9eWtZCx3vpwkNSvTuWcxJsukYpTw.mail.gmail.com
> <mailto:CAA5VDpDSCstP8vGa_cQ3Nj9eWtZCx3vpwkNSvTuWcxJsukYpTw.mail.gmail.com
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> > CAA5VDpDSCstP8vGa_cQ3Nj9eWtZCx3vpwkNSvTuWcxJsukYpTw.mail.gmail.com
> <mailto:CAA5VDpDSCstP8vGa_cQ3Nj9eWtZCx3vpwkNSvTuWcxJsukYpTw.mail.gmail.com
> >>>
> > Content-Type: text/plain; charset="UTF-8"
> >
> > Hello,
> >
> > One of my students noticed that their simulations were running much more
> > slowly suddenly, and when looking at our tleap output we observed that
> the
> > solvateoct command seems to be adding a significantly larger number of
> > water molecules to the system than it has in the past (with the same
> > padding value, using the same initial structure). We went back and
> checked
> > the behavior in 25,24,23,22 versions and they were all consistent with
> the
> > number of water molecules being placed by solvateoct. Has there been some
> > change in the way solvateoct handles building the water shell?
> >
> > Thanks!
> > Joe
> >
> > ------
> > Joseph Baker, PhD
> > Barbara Meyers Pelson Chair in Faculty-Student Engagement (AY 2024-2027)
> > Professor, Department of Chemistry
> > The College of New Jersey
> > Ewing, NJ 08628
> > Chair-elect (2026), Trenton Local Section of the ACS
> > Chemistry Division Representative (2024-2027), The Council on
> Undergraduate
> > Research
> >
> >
> > ------------------------------
> >
> > Subject: Digest Footer
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Received on Thu Jun 18 2026 - 12:30:03 PDT
