Thank you prof. Case and prof. Cheatham,
In the following, we've included the standard errors (SE, expressed in
kcal/mol) for the bound and unbound dG simulations (derived from 5
replicates each)
system1: 0.71 (amber20, bound SE: 0.46, unbound SE: 0.28), -0.23 (amber22,
bound SE: 0.33, unbound SE: 0.39), 1.15 (empirical)
system2: 0.55 (amber20, bound SE: 0.18, unbound SE: 0.03), -0.17 (amber22,
bound SE: 0.24, unbound SE: 0.18), 0.83 (empirical)
system3: 2.35 (amber20, bound SE: 0.29, unbound SE: 0.68), -0.05 (amber22,
bound SE: 0.90, unbound SE: 0.43), 3.15 (empirical)
system4: 3.96 (amber20, bound SE: 0.93, unbound SE: 1.01), 1.29 (amber22,
bound SE: 1.16, unbound SE: 0.50), 5.59 (empirical)
system5: 2.58 (amber20, bound SE: 1.10, unbound SE: 0.67), 3.39 (amber22,
bound SE: 0.79, unbound SE: 1.13), 5.82 (empirical)
As prof. Case suggested, our primary concern is whether amber20 and amber22
are yielding different results during alchemical free energy calculations.
The differences between amber predictions and empirical benchmarks are
secondary for us and can be discussed later.
We will run a short simulation using either amber20/amber22, starting from
a common restart, using the same ig value and on the same GPU node (we're
not sure if the same GPU node is necessary for deterministic
trajectories... but just in case). After reviewing the mdout's of amber20
vs amber22 carefully, we will report back.
mike and skanda
p.s. good catch on nstlim of 0.7 ns. We probably should've chosen a better
example script input file. this particular run had been pre-empted on our
cluster after 4.3 ns and we were running the remaining 0.7 ns. Each of our
12 production lambdas are 5 ns.
On Sun, Feb 5, 2023 at 9:02 AM David A Case via AMBER <amber.ambermd.org>
wrote:
> On Fri, Feb 03, 2023, Thomas Cheatham via AMBER wrote:
> >
> >> We are struggling to achieve comparable results when performing the same
> >> alchemical free energy protocols using amber2020 versus amber2022 (our
> >
> >...
> >>
> >> below results are ddG, expressed in kcal/mol
> >> system1: 0.71 (amber20), -0.23 (amber22), 1.15 (empirical)
> >> system2: 0.55 (amber20), -0.17 (amber22), 0.83 (empirical)
> >> system3: 2.35 (amber20), -0.05 (amber22), 3.15 (empirical)
> >> system4: 3.96 (amber20), 1.29 (amber22), 5.59 (empirical)
> >> system5: 2.58 (amber20), 3.39 (amber22), 5.82 (empirical)
> >
> >
> >Never trust a single run. You likely need multiple replicates
>
> The original post already indicated that 5 replicates had been made. But
> it
> might be useful to know how different the individual runs are from the
> averages shown above. That would give a bit of a clue about how much the
> sampling errors might be.
>
> The input file had a but of a funny comment:
>
> nstlim=700000,!5ns production run
>
> nstlim shows a 0.7 ns run, but the comment says 5 ns. We don't know if you
> made many such runs for each lamda value or not.
>
> The key point (I think) is that amber20 and amber22 seem to be giving
> different results. (The empirical results are so far from either Amber
> results that I would set them aside for the moment.)
>
> One other test: with the same restart file, and fixing the ig value, run
> parallel short runs with Amber20 vs Amber22, printing every step (ntpr=1).
> Do you see any differences between the two codes.
>
> I'm cc-ing this to Taisung in case he has thoughts about whether any
> defaults in Amber22 are different from those in Amber20. But carefully
> compare an mdout file from the two programs (say with vimdiff or some other
> editor that can look at two files at once.) Look at the output before the
> first step with an eagle eye, to try to spot anything that might be
> relevant
> difference between the two sets of runs.
>
> ....regards...dac
>
>
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Received on Mon Feb 06 2023 - 14:00:02 PST
