Re: [AMBER] Advice on Simulated Annealing

From: Hector A. Baldoni <>
Date: Thu, 30 Dec 2021 13:50:38 -0300

Dear Matthew,

For loops optimizations you could try ibelly constrained positions of
your protein backbone (except loops of interest) plus simulated
annealing of the loops of interest locally enhanced defined. This
procedure gave me good results in loops optimizations of human AT2
receptor. I lost your original query, so I apologize if it is not what
you were asking.


El 2021-12-30 13:00, Matthew Guberman-Pfeffer escribió:
> 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.
> Best,
> Matthew
>> 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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  Dr. Hector A. Baldoni
  Profesor Titular (FQByF-UNSL)
  Investigador Adjunto (IMASL-CONICET)
  Area de Quimica General e Inorganica
  Universidad Nacional de San Luis
  Chacabuco 917 (D5700BWS)
  San Luis - Argentina
  hbaldoni at unsl dot edu dot ar
  Tel.:+54-(0)266-4520300 ext. 6157
First things first, but not necessarily in that order.
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Received on Thu Dec 30 2021 - 09:00:02 PST
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