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 <david.case.rutgers.edu> 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.
>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> https://nam10.safelinks.protection.outlook.com/?url=http%3A%2F%2Flists.ambermd.org%2Fmailman%2Flistinfo%2Famber&data=04%7C01%7C%7Ce27a5093ff3d44ca502a08d9cb406ab6%7C17f1a87e2a254eaab9df9d439034b080%7C0%7C0%7C637764299793150857%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=jZh8vNazqevBWwiVEj%2BNAN5rjNNFwImaXJuxeM86Gdg%3D&reserved=0
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Thu Dec 30 2021 - 08:30:02 PST
