Re: [AMBER] Advice on Simulated Annealing

From: Matthew Guberman-Pfeffer <>
Date: Thu, 30 Dec 2021 11:00:57 -0500

Thanks, David, for the advice. I learned yesterday before seeing your reply that indeed high temperatures without any restraints will cause the protein to ‘explode’ quite spectacularly.
I also assumed that ordinary MD wouldn’t be sufficient, but I’m glad you suggested seeing how that goes first before experimenting with accelerated sampling techniques.


> On Dec 29, 2021, at 9:59 PM, David A Case <> wrote:
> *Message sent from a system outside of UConn.*
> On Wed, Dec 29, 2021, Matthew Guberman-Pfeffer wrote:
>> I’m wondering if advice can be offered on how to select the maximum
>> temperature and heating/cooling schedules for simulated annealing.
> If you don't have restraints on a protein, you probably need to keep the
> maximum temperature pretty low (e.g. 300K): if your protein starts to unfold
> (even locally) during the run, cooling is unlikely to bring it back to
> a good structure.
> If you can afford it, I'd suggest starting with something like 10 ns: say
> run at 300K for 5 ns, and cool to zero over another 5 ns. Then see if you
> get better/differnt results by doubling the time. (I use nmropt=1 to slowly
> change TEMP0 from 300 to 0 during the second half of the run.
> If you know where the strain is (e.g. between the porphyrin rings), you
> could restrain parts of the system away from the problem area. Then you
> could probably accommodate a higher maximum temperature. (You might want to
> always restrain things that are far from the added porphyrins, on the
> hypothesis that alphafold generally knows what it's doing.)
> These are all guesses, based on limited experience, and others may
> have their own anecdotes, or know of more systematic explorations. And
> there are certainly many other accelerated sampling approaches that could be
> used. But just letting the system rattle around for a while with MD will
> often do wonders for localized strain.
> ....dac
> Caveat: when I suggest protocols like the above to my students, it's pretty
> common to find out that my advice wasn't very good.
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Received on Thu Dec 30 2021 - 08:30:02 PST
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