Hi Fanyu,
sorry to hear igb=0 didnt work, but have you checked running the same job
using pmemd or sander on CPU? If it segfaults there as well, it likely is
something about the input you are using. If you want to make sure the
charge change is the source of the problem, could you try the same
calculation with a protonated Asp, just to check your input (plus one H)
works in that case?
I still dont understand what you need the vacuum simulation for, if this is
about peptide binding, then you would normally simulate the peptide
transformation in solvent and bound to whatever it is binding to. A vacuum
TI transformation is only needed if you care about the change in solvation
free energy (from ddG(TI,solv) - ddG(TI,vac) ) and since that is probably
not something experimentally accessible for a peptide, what would you use
the result for?
If you really care about this transformation in vacuum, it may be hard to
get a meaningful answer. Changing a charge in vacuum is not the same as
changing it in a periodic boundary environment, due to the charge-charge
interactions between periodic images, so your thermodynamic cycle doesnt
quite close. I'm not 100% sure what the current best practice is to handle
such cases, but the alchemical ion approach is intended to get rid of such
box size effects. Since the alchemical ion approach does not work in
vacuum, Id stear clear of total system charge changes for such a case.
Kind Regards,
Thomas
On Mon, Jun 5, 2023 at 9:42 AM Fanyu Zhao <fz2113.nyu.edu> wrote:
> Hi Thomas,
>
> Thanks for your reply!
>
> Yes, I tried using igb=0, and the simulation just stopped at reading
> restart file. The error message gives a segmentation fault so I think there
> might be something wrong with the input file I'm using.
>
> Actually, I'm trying to calculate the relative binding free energy of a
> peptide mutation involving charge-changing (e.g. mutating Asp to Ala, with
> the charge changing from -1 to 0). So far I've tried using co-alchemical
> ions to balance the charge between the two systems, or running the
> simulation without any correction of the changed charge. Both failed.
>
> So I'm thinking if I could firstly calculate the energy change of mutation
> on gas phase, and secondly calculate the solvation energy difference of the
> wild-type and mutant, and then sum the two terms up.
>
> I cannot figure out any other methods in TI to calculate the mutation
> involving charge-changing :(. It would be appreciated if you could give me
> any suggestions on this.
>
> Best,
> Fanyu
>
> On Mon, Jun 5, 2023 at 3:29 PM Steinbrecher, Thomas <
> thomas.steinbrecher.roche.com> wrote:
>
>> Hi Fanyu,
>>
>> have you tried running with igb = 0 ? It should be the same effect as
>> igb=6 based on what I see in the manual, but maybe there is a check in
>> pmemd about "igb > 0" that is missing that igb = 6 would also correspond to
>> vacuum?
>>
>> As a side note, based on the masks, you seem to have a 10+ residue
>> peptide in your simulation, are you sure a vacuum simulation of this
>> species is meaningful?
>>
>> Kind Regards,
>>
>> Thomas
>>
>> On Mon, Jun 5, 2023 at 4:26 AM Fanyu Zhao via AMBER <amber.ambermd.org>
>> wrote:
>>
>>> Dear amber users,
>>>
>>> I'm trying to run TI in the gas phase. But it always gives me an error
>>> message of "The CUDA code currently cannot handle TI with implicit
>>> solvent
>>> models! Please use the serial code instead".
>>>
>>> I was wondering if gas phase TI can only be performed with CPU and if I'm
>>> correct with the process of creating a pdb file in gas phase.
>>>
>>> Here's my input for a minimization.
>>>
>>> Minimization with position restraint
>>> &cntrl
>>> imin = 1, ntmin = 2, maxcyc = 10000,
>>> ntpr = 1000, ntwe = 1000,
>>> ntr = 1, restraint_wt = 100.0,
>>> restraintmask = '!.H= ',
>>> ntb=0,igb=6, cut = 9999.0, ioutfm = 1,
>>> icfe = 1, ifsc = 1, logdvdl = 0,
>>> timask1=':10',
>>> timask2=':3',
>>> scmask1=':10 & !.CA,C,N,O',
>>> scmask2=':3 & !.CA,C,N,O',
>>> clambda=0.5,
>>> &end
>>> /
>>>
>>>
>>> And here's the tleap file I used to generate a gas phase pdb file.
>>>
>>> source leaprc.protein.ff14SB
>>>
>>> com=loadpdb 1tvb_aftermd.pdb
>>> unbound=loadpdb peptide.pdb
>>>
>>> savepdb com wild_md_bound.pdb
>>> saveamberparm com wild_md_bound.prmtop wild_md_bound.inpcrd
>>>
>>> savepdb unbound wild_md_unbound.pdb
>>> saveamberparm unbound wild_md_unbound.prmtop wild_md_unbound.inpcrd
>>> quit
>>>
>>>
>>> Thank you so much!
>>>
>>> Best,
>>> Fanyu
>>> _______________________________________________
>>> AMBER mailing list
>>> AMBER.ambermd.org
>>> http://lists.ambermd.org/mailman/listinfo/amber
>>> <https://urldefense.proofpoint.com/v2/url?u=http-3A__lists.ambermd.org_mailman_listinfo_amber&d=DwMFaQ&c=slrrB7dE8n7gBJbeO0g-IQ&r=TA6Yv1GqGslhLaifgggoUQ&m=4WjHVK2ypm7vH0Okye8p2Ny0JAsKRcIz9NXV9bVSYGgs24GTPqJvmd0_PYIvgSFY&s=jj3P4Wq5mxqWq6hYdbE91qLTi7Stm6DKikZPbRtmspw&e=>
>>>
>>
>>
>> --
>> *Dr. Thomas Steinbrecher*
>> Principal Scientist CADD
>>
>> Roche Pharma Research and Early Development
>> Roche Innovation Center Basel
>> F. Hoffmann-La Roche Ltd
>> Bldg. 092/3.92
>> Grenzacherstrasse 124
>> 4070 Basel
>> Switzerland
>>
>> Phone +41 61 682 1319
>> mailto: thomas.steinbrecher.roche.com
>>
>
--
*Dr. Thomas Steinbrecher*
Principal Scientist CADD
Roche Pharma Research and Early Development
Roche Innovation Center Basel
F. Hoffmann-La Roche Ltd
Bldg. 092/3.92
Grenzacherstrasse 124
4070 Basel
Switzerland
Phone +41 61 682 1319
mailto: thomas.steinbrecher.roche.com
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Received on Mon Jun 05 2023 - 01:30:02 PDT
