Re: AMBER: Do I need to repeat MD simulation?

From: bishop <>
Date: Wed, 21 Jan 2004 09:14:45 -0600

What Bob said is true. And what Andreas said it true.
But the question remains how does one determine significance of the

This all depends on what you are looking for: hardware, software or
system (model) dependencies in your results.

1) Differences due to numerical computing (order of operations type
issues) should be in the 5th or 6th decimal place and affected by
physical nature of the machine, compiler, etc....
(amber is single precision right?).
These are significant if you are of a hardware mindset

2) Differences due to numerical methods, e.g the integration step size,
PME considerations, etc... all have an effect on the fluctuations of
solutions. These fluctuations may be equal to or significantly greater
than numerical precision.
These are significant if you are of a software/methods mindset.

3) Differences due to initial assignment of velocities (random number
seed issues) should be on the order the kinetic energy fluctuations
observed during run time in your system. This has to be at least as
great as the fluctuations due to numerical methods, but should vary with
(Square root ?) of the number of particles in the system. The
dependence of the fluctuation on the nature of the system is what makes
these fluctuations different from 2).
These are significant to the biologists.

I expect differences in 2) to be greater than differences in 1) but it
depends on your choice of simulation parameters. I expect 3) > 2) but
it depends on the details of your system.

If your "significant result" is biological shouldn't it depend on 3) and
not 2) or 1)?

If the significant result only depends on 3) then you can run multiple
simulations or longer simulations to determine a probability of it
happening as a measure of significance. You can also perturb your result
by changing not only the temperature but charge assignments, bond
strenghts, etc... (as in FEP calculation) to find the underlying source
for the event.

Differences due to 1) and 2) are often ignored and simply replaced by a
rule of thumb (like 2fs timestep with shake) but only if 1) and 2) are
excluded does 3) carry any significance. Granted isolating each of
these is no small undertaking.

Just my $.03, which is admittedly $.01 more than warranted.
Please add/subtract/agree/disagree with me.


Robert Duke wrote:

> It should also be noted that same executable + same random seed + same
> architecture WON'T produce the same results on parallel runs (ie., under
> mpi). This has to do with order of operations issues in the networking, at
> a minimum, and loadbalancing issues, where it is used in programs like
> pmemd.
> Regards - Bob
> ----- Original Message -----
> From: "Andreas Svrcek-Seiler" <>
> To: <>
> Sent: Wednesday, January 21, 2004 5:40 AM
> Subject: Re: AMBER: Do I need to repeat MD simulation?
>>> A general question.Do I need to repeat my simulation several times to
>>>prove the changes of protein I observed significant, not some artifical
>>...Definitely, if the change is "irreversible".
>>If the changes are "reversible", like repeated folding and unfolding
>>(that would be a cool observation)
>>or repeated conversions between well defined distinct conformations,
>>you might simply continue the existing trajectory for a much longer time.
>>Generally, don't accept the outcome of MD simulations as proof for
>>anything (or be *very* cautious at least).
>>>And will two trajectory files be identical if I run twice with
>>>identical input files?
>>...Same executable + same random seed + same architecture: yes.
>>Executable compiled with different compiler options (or another
>>compiler): trajectories might slowly diverge from each other.
>>Different random seeds (i.e. identical coordinates but not completely
>>identical input files): No.
>>However, relevant results must be independent of the random seed.
>>...just my 0.02%
>> )))))
>> (((((
>> ( O O )
> -
>> o Wolfgang Andreas Svrcek-Seiler
>> o (godzilla)
>> .oooO Tel.:01-4277-52733
>> ( ) Oooo.
> ---( )--------------------------------------------------------
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Received on Wed Jan 21 2004 - 15:53:01 PST
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