Re: AMBER: comparison of MD trajectories recorded with pmemd and sander

From: Adrian Roitberg <>
Date: Wed, 17 Dec 2008 11:40:23 -0500

I will try to answer this in a slightly convoluted way.

Molecular dynamics trajectories are inherently chaotic. This means that
the trajectory is extremelly dependent on initial conditions.

A useful exercise to do is this:

Run an MD trajectory with the software, force, temperature and molecule
of your choice for X ns.
Run a second trajectory with ALL variables the same as above, but with a
the change in the coordinates of ANY atom in just one component (x,y or
z) by ONE unit in the last decimal place in your input file.
This is as minimal a perturbation as you can make.

Compare how long does it take for the two trajectories to 'diverge' from
each other in some measure (RMSD against each other, frame by frame for
instance). It usually takes around 5 picoseconds to get away by as much
as 0.5 A RMSD for 100 atoms.

Note that this is WAY shorter that the MD we run these days.

Now, let's ask your question:
Is trajectory 1 better or worse than trajectory 2 ?
Obviously, they are equally good (or bad ;-))

That said: yes, the trajectories coming from different programs are
homogeneous in your sense. You can run in one program for a bit, save
data and keep running on another. There is no basic problem with this.

Now for the catch:
For all the above text to be correct, you MUST get the same energy and
forces, to machine precision, if you take single structures and run them
in different programs.

So, can you take 1000 structures generated with sander and compute
single point energies and forces with the SAME input in pmemd and expect
the same values ? Absolutely, Bob Duke has worked hard to make this
happen !
(he will answer shortly that this is not strictly true, but trust me, we
have checked)

Can you take 1000 structures generated with sander and compute single
point energies and forces with the SAME input in NAMD (using the same
amber force field) and SHOULD YOU expect the same values ? Absolutely !

Would you get the same values ? Good luck with that one !!!
I am pretty sure you would not ! The amber force field implementation
in namd is obscure at best, and there are some flags you need to set up
in the input to make it all work.

Just my 2.5 cents worth of advice for today


� wrote:
> Dear Prof. Duke,
> I am sorry for having forced you to answer again to questions you
> already discussed in the past in the AMBER discussion list.
> The purpose of my mail is not to question the enormous work which was
> put into the pmemd development, and I am perfectly convinced that this
> program does bring certainly a lot to the AMBER package.
> But, I am concerned by the following problem. Molecular modeling studies
> are often based on the comparison of MD trajectories run with several
> conditions. In that way, two sander trajectories are recorded
> with different conditions and compared. If one trajectory is recorded with
> pmemd, and the other with sander, is the comparison still meaningful?
> Also, if one uses an additional trajectory recorded by CHARMM, GROMACS
> or NAMD with the AMBER force-field, will the pmemd trajectory be
> "closer" to the sander trajectory than the CHARMM, GROMACS or NAMD
> trajectory?
> If two trajectories are recorded with pmemd and sander starting from the
> same input, should we consider that they are no more different than
> two trajectories recorded with the same program (sander or pmemd) but
> using different initial velocities?
> Another question is: let one suppose that a trajectory was recorded
> using alternatively sander and pmemd for different time intervals, in
> the following way: some ns with pmemd, then restart with keeping velocities
> and then additional ns with sander. Should the complete trajectory
> obtained with these different interval be considered as an "homogeneous"
> trajectory which can be analyzed as a whole?
> I am sorry for insisting on these questions, but they are important for
> me in order to plan future calculations. I hope that I do not waste too
> much your time. Also, I realize that it is probably difficult to answer
> these questions, except by doing tests on each studied system, but I am
> just interested to read your opinion about these points.
> Best regards,
> Therese Malliavin
> Unite de Bioinformatique Structurale
> Institut Pasteur, Paris
> France
> On Tue, 16 Dec 2008, Robert Duke wrote:
>> Okay, this has been discussed a lot. PMEMD should replicate sander
>> results for a couple of hundred steps at least, unless you have an
>> unbelievably bad starting configuration with a couple of atoms on top
>> of each other (in which case some of the force gradients are huge and
>> the simulation is bad anyway). However, the thing with MD is that
>> there are on the order of millions, if not billions, of calculations
>> per step, including additions, and the thing about addition of
>> floating point numbers on computers is that it is not truly
>> associative - the order in which the additions are performed DOES
>> matter, due to truncation in the floating point representation of the
>> number. So what this means is that if you have an algorithm that is
>> different AT ALL, even in logically insignificant ways, there will be
>> a rounding error, and due to the nature of MD, this rounding error
>> will rather quickly grow. The main sources of difference between
>> pmemd and sander are probably the following: 1) a different splining
>> function for the erf() function in pmemd for some implementations
>> (there is an optimization, and pmemd is actually more accurate than
>> sander), 2) workload distribution differences running in parallel
>> (which effect which force additions will occur with net-limited
>> precision of a 64 bit floating point number), and 3) differences in
>> the order of force additions arising from differences in calculation
>> and communication order. The thing to note about rounding error - we
>> are talking about a loss in precision down around 1e-17 I believe -
>> rather small. Now, the erf() splining errors are probably closer to
>> 1e-11 - probably the lowest precision transcendental we have, but the
>> other transcendental functions are probably between these two numbers
>> in precision (rough guess, have not looked recently, and it will be
>> machine-dependent). Now all this junk does not really matter, because
>> your calculation is probably off by at least 1e-5 (actually much
>> worse) based on precision of forcefield parameterization, the fact
>> that coulomb's law does not really get electrostatics just right, the
>> fact that (substitute here the next force term generator) just right,
>> ... And the standard justification for not being disturbed by all this
>> - the different errors just mean that you sample different parts of
>> phase space, and if you run long enough, you will get it all (this
>> last point is why I have labored so long to make pmemd fast). Run
>> your system on some other software and you will see some more dramatic
>> differences in phase space sampling... Heck, just change the cutoffs
>> a bit, the fft grid densities, etc. etc. etc. I have gone on-and-on
>> about this stuff for the last several years on the amber reflector
>> (see for links), probably hitting different high and low
>> points - perhaps worth going back to look over, if you want the
>> complete discussion. I always jump on these questions, but am sort-of
>> answering for Ross here because I am 3 hrs closer to Europe and he is
>> hopefully still asleep ;-)
>> Regards - Bob Duke
>> ----- Original Message ----- From: "Th�r�se Malliavin" <>
>> To: <>
>> Sent: Tuesday, December 16, 2008 7:57 AM
>> Subject: RE: AMBER: launching a job works with sander.MPI and fail
>> with pmemd.MPI
>> Hi Ross,
>> Thank you for your mail. Finally, I tried to use AMBER 10 in place of
>> AMBER 9, and pmemd runs without any problem. Now, I have another naive
>> question. I already realized that pmemd runs significantly faster than
>> sander even on 4 processors. But, if I compare the results obtained
>> by sander and pmemd starting from the same system, as for example the
>> total energy, the two runs seem not to be so much correlated. So, I would
>> like to know whether we have to expect that pmemd or sander should
>> produce
>> the same numbers if the runs start from the same system. The
>> differences observed come probably from a different architecture of the
>> two programs, could you please tell me little bit more about that?
>> Thank you for your help,
>> Best regards,
>> Therese
>> On Mon, 15 Dec 2008, Ross Walker wrote:
>>> Hi Therese,
>>> First thing to check. PMEMD when built in parallel (which I assume
>>> you did)
>>> is called pmemd, not pmemd.MPI. Hence you should be getting a file
>>> not found
>>> error - which in parallel may be masking itself as a lamboot failure.
>>> Also I would make sure you do the following to run cleanly in your
>>> script:
>>> export AMBERHOME=/foo/bar/amber10
>>> lamboot
>>> mpirun -np 4 $AMBERHOME/exe/pmemd -O -i ...
>>> lamhalt
>>> Then you can nohup the entire script. You should probably make sure
>>> you kill
>>> any existing lambood or lamd instances on your machine first though
>>> since
>>> some will probably be left over from earlier runs. You should also
>>> make sure
>>> that pmemd was built with the same version of lam as your mpirun
>>> refers to.
>>> Makes sure you run the test cases:
>>> export DO_PARALLEL='mpirun -np 4'
>>> lamboot
>>> cd $AMBERHOME/test/
>>> make test.pmemd
>>> lamhalt
>>> Good luck,
>>> Ross
>>>> -----Original Message-----
>>>> From: [] On
>>>> Behalf
>>>> Of Th�r�se Malliavin
>>>> Sent: Monday, December 15, 2008 6:42 AM
>>>> To:
>>>> Cc:
>>>> Subject: AMBER: launching a job works with sander.MPI and fail with
>>>> pmemd.MPI
>>>> Dear AMBER Netters,
>>>> I have a question about the use of PMEMD. It is probably a trivial
>>>> question, but, as I did not find an answer neither on the Web pages
>>>> neither in the manuals, I am asking it to you.
>>>> I am doing the parallel calculations with sander.MPI using a lamd
>>>> deamon
>>>> and the command nohup to launch the job, so I am doing:
>>>> . /Bis/shared/centos-3_x86_64/etc/custom.d/amber9_intel8.1_lam-
>>>> lamboot
>>>> before starting the AMBER calculations. The typical command line for
>>>> sander.MPI is then:
>>>> mpirun -np 4 ${AMBERHOME}/exe/sander.MPI -O -i -o mdr1.out -inf
>>>> mdr1.inf -x mdr1.crd -c eq7.rst -p prmtop -r mdr1.rst
>>>> But, if I replace in the command line sander.MPI by pmemd.MPI:
>>>> mpirun -np 4 ${AMBERHOME}/exe/pmemd.MPI -O -i -o mdr1.out -inf
>>>> mdr1.inf -x mdr1.crd -c eq7.rst -p prmtop -r mdr1.rst
>>>> I get an error saying that lamboot was not started.
>>>> I am trying to do these calculation on an 64 bits 8-proc Linux machine,
>>>> running under centos-3. The lam used is the version 7.1.2_intel-8.1.
>>>> Also, I am only using features which should exist in PMEMD according to
>>>> the AMBER manual.
>>>> Do you have any idea what I could check or what to find information
>>>> to fix
>>>> this problem?
>>>> Thank you in abvance for your help,
>>>> Therese Malliavin
>>>> Unite de Bioinformatique Structurale
>>>> Institut Pasteur, Paris
>>>> France
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                            Dr. Adrian E. Roitberg
                              Associate Professor
                             Quantum Theory Project
                            Department of Chemistry
                  Senior Editor. Journal of Physical Chemistry
                           American Chemical Society
University of Florida                         PHONE 352 392-6972
P.O. Box 118435                               FAX   352 392-8722
Gainesville, FL 32611-8435                    Email
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Received on Fri Dec 19 2008 - 01:09:35 PST
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