As Carlos mentioned, you cannot compare energies of different molecular systems that are not directly the same composition. But, if you built a system with the ion-protein bound vs. ion-free with exactly the same number of waters you could compare energies, but this requires a large number of frames and is very noisy. We did this in this work with explicit water included: http://pubs.acs.org/doi/abs/10.1021/ci500132c and also this work in an MM-PBSA context: https://www.cell.com/biophysj/fulltext/S0006-3495(03)74608-6
-tec3
> I think I understand the point Carlos mentioned.
> I'm getting meaningful continuum solvation energy differences after
> stripping the water and ions.
> But I'm still trying to understand if there's some way to estimate the
> differences in solvent and protein reorganization energies between two
> states with just one charge difference using the explicit solvent MD
> trajectories.
>
> Looking forward to receiving valuable suggestions and advice from the list.
> Thanks for the valuable suggestions and comments.
> Best regards.
>
> On Sat, Oct 3, 2020, 18:46 Carlos Simmerling <carlos.simmerling.gmail.com>
> wrote:
>
>> In general, molecular mechanics absolute energies cannot be compared for
>> different molecules or systems. The zero is arbitrary and only relative
>> energies of a given system are meaningful. The conformations sampling can
>> be compared, using the methods discussed earlier in this thread.
>>
>> On Fri, Oct 2, 2020, 5:12 PM Vaibhav Dixit <vaibhavadixit.gmail.com>
>> wrote:
>>
>>> Dear all,
>>> This is troubling since it seems to kill the very purpose for which I
>>> started to build the two states for the system.
>>> Moreover the assumption that they have equal number of water molecules
>> also
>>> seems incorrect because while adding the extra ion to neutralize the
>> system
>>> tleap must have removed some water molecules that are present in the
>>> trajectory.
>>>
>>> I think it is possible to add equal number of ions in both the systems.
>>> That will keep the number of water molecules also same and make the
>> energy
>>> comparable. But I'm not sure if I it is meaningful to simulate a system
>>> with net 1 negative charge. Will it create instabilities during the MD
>>> simulations? Are sander and pmemd and other tools expected to handle this
>>> correctly? I think so but can someone please confirm.
>>>
>>> Please suggest and help me decide the best possible way to simulate the
>>> charge difference and the estimate difference in other measurable
>>> properties.
>>>
>>> Thank you and best regards.
>>> Vaibhav
>>>
>>> On Fri, Oct 2, 2020, 22:01 Carlos Simmerling <
>> carlos.simmerling.gmail.com>
>>> wrote:
>>>
>>>> I'm not sure I see a way to compare energies, the extra ion will
>> interact
>>>> with everything else due to PME, and if you delete it you'll have a
>> hole
>>>> that the other system won't have that likely will shift the energies
>> for
>>>> the water. You could strip all water and ions and compare energies in a
>>>> continuum model, but you'd need to decide if that approximation is ok
>> or
>>>> not.
>>>> maybe others have better ideas here...
>>>> carlos
>>>>
>>>> On Fri, Oct 2, 2020 at 11:42 AM Vaibhav Dixit <vaibhavadixit.gmail.com
>>>
>>>> wrote:
>>>>
>>>>> Dear All,
>>>>> these are helpful suggestions, thanks Carlos,
>>>>> After these commands, I assume that, if I load the trajectory for
>> the
>>>> 2nd
>>>>> structure and give similar rmsd commands, I should be able to see how
>>> it
>>>>> evolves during MD simulation, right? Then I hope I can see/compare
>> them
>>>> in
>>>>> one plot may be using gnuplot (xmgrace is not working on my Centos
>> 7).
>>>>>
>>>>> How can I handle this incompatibility between prmtops while
>> estimating
>>>> the
>>>>> Es with imin=5 of one structure with parameters for the other
>>> (parameters
>>>>> are different only for the co-factor and residues coordinating with
>> it
>>> in
>>>>> addition to the difference of the extra ion)?
>>>>>
>>>>> I hope that these questions are meaningful and I'll get valuable
>>>>> suggestions to tackle the same.
>>>>>
>>>>> Thank you and best regards :)
>>>>> Vaibhav
>>>>>
>>>>> On Fri, Oct 2, 2020 at 8:37 PM Carlos Simmerling <
>>>>> carlos.simmerling.gmail.com> wrote:
>>>>>
>>>>>> cpptraj will allow you to specify a different prmtop and
>>>>>> reference coordinate set when doing RMSD calculations... it can get
>>>>>> complicated if atoms don't match up, but your case sounds like a
>>> single
>>>>>> atom mask will give the same selection for both systems so it
>> should
>>>> work
>>>>>> smoothly. Dan Roe or others might have more detailed advice, but
>> this
>>>>> works
>>>>>> for me.
>>>>>>
>>>>>> I use something like this in my cpptraj script.
>>>>>> load both prmtops, with a label for the alternate one
>>>>>>
>>>>>> parm ./prmtop
>>>>>> parm ../build_40/prmtop [refparm]
>>>>>>
>>>>>> define reference structures, indicating the alternate prmtop for
>> the
>>>>> other
>>>>>> system, and label each reference structure for use later:
>>>>>>
>>>>>> reference ./1min.rst7 [refinit]
>>>>>> reference ../build_40/struct40.rst7 parm [refparm] ref [ref40]
>>>>>>
>>>>>> trajin ./md.x
>>>>>>
>>>>>> calculate rmsd to the SAME system:
>>>>>>
>>>>>> rmsd rms1 :10-70.CA,N,C,O out rmsd.10-70.dat ref [refinit]
>>>>>>
>>>>>> and then when doing the rmsd to the alternate system:
>>>>>>
>>>>>> rmsd rms2 :10-70.CA,N,C,O out rmsd.10-70.ref40.dat ref [ref40]
>>>>>>
>>>>>> On Fri, Oct 2, 2020 at 10:56 AM Vaibhav Dixit <
>>> vaibhavadixit.gmail.com
>>>>>
>>>>>> wrote:
>>>>>>
>>>>>>> Dear Amber developers and users,
>>>>>>> I have two structures identical except for a difference in
>>> co-factor
>>>>>>> charge.
>>>>>>> Thus one has a Cl- ion extra added by tleap, but the number of
>>>>>>> protein, non-standard residue and water atoms are identical.
>>>>>>> Now, how do I compare the rmsd of the two trajectories snapshot
>> by
>>>>>>> snapshot?
>>>>>>> Both trajectories start from the same PDB, thus I want to check
>> if
>>>> (how
>>>>>>> much) there is a divergence in the coordinate-space that they
>>> sample
>>>> as
>>>>>>> they move along the MD trajectories.
>>>>>>> Is it possible/meaningful to compare reorganization of waters and
>>> AA
>>>>>>> between the two trajectories w.r.t. to coordinates and energies?
>>> As
>>>>>>> suggested earlier I will try to use imin=5 for this, but first I
>>>> think
>>>>> I
>>>>>>> need to resolve incompatibility due to the extra Cl- ion. Both
>> Cl-s
>>>>> are >
>>>>>>> 10 A from cofactor, so is it safe to simply ignore them and
>> delete
>>>> from
>>>>>>> both prmtop before rmds or other analysis?
>>>>>>>
>>>>>>> I tried to use cpptraj to estimate rmsd for one trajectory using
>>>> prmtop
>>>>>> of
>>>>>>> another which failed (then realized the small but important
>>>> difference
>>>>>>> between the two).
>>>>>>> Is it possible to simply delete the extra/both Cl- from prmtop
>> with
>>>>>> parmed
>>>>>>> and will it then work with cpptraj for all kinds of analysis.
>>>>>>> Please suggest.
>>>>>>> Looking forward to valuable suggestions from the list on this.
>>>>>>> thank you and best regards.
>>>>>>>
>>>>>>>
>>>>>>> --
>>>>>>>
>>>>>>> Regards,
>>>>>>>
>>>>>>> Dr. Vaibhav A. Dixit,
>>>>>>>
>>>>>>> Visiting Scientist at the Manchester Institute of Biotechnology
>>>> (MIB),
>>>>>> The
>>>>>>> University of Manchester, 131 Princess Street, Manchester M1 7DN,
>>> UK.
>>>>>>> AND
>>>>>>> Assistant Professor,
>>>>>>> Department of Pharmacy,
>>>>>>> ▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄
>>>>>>> Birla Institute of Technology and Sciences Pilani (BITS-Pilani),
>>>>>>> VidyaVihar Campus, street number 41, Pilani, Rajasthan 333031.
>>>>>>> India.
>>>>>>> Phone No. +91 1596 255652, Mob. No. +91-7709129400,
>>>>>>> Email: vaibhav.dixit.pilani.bits-pilani.ac.in,
>>>> vaibhavadixit.gmail.com
>>>>>>> http://www.bits-pilani.ac.in/pilani/vaibhavdixit/profile
>>>>>>> https://www.linkedin.com/in/vaibhav-dixit-b1a07a39/
>>>>>>>
>>>>>>> ORCID ID: https://orcid.org/0000-0003-4015-2941
>>>>>>>
>>>>>>>
>>> http://scholar.google.co.in/citations?user=X876BKcAAAAJ&hl=en&oi=sra
>>>>>>>
>>>>>>> P Please consider the environment before printing this e-mail
>>>>>>> _______________________________________________
>>>>>>> AMBER mailing list
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>>>>>>
>>>>>
>>>>>
>>>>> --
>>>>>
>>>>> Regards,
>>>>>
>>>>> Dr. Vaibhav A. Dixit,
>>>>>
>>>>> Visiting Scientist at the Manchester Institute of Biotechnology
>> (MIB),
>>>> The
>>>>> University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
>>>>> AND
>>>>> Assistant Professor,
>>>>> Department of Pharmacy,
>>>>> ▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄
>>>>> Birla Institute of Technology and Sciences Pilani (BITS-Pilani),
>>>>> VidyaVihar Campus, street number 41, Pilani, Rajasthan 333031.
>>>>> India.
>>>>> Phone No. +91 1596 255652, Mob. No. +91-7709129400,
>>>>> Email: vaibhav.dixit.pilani.bits-pilani.ac.in,
>> vaibhavadixit.gmail.com
>>>>> http://www.bits-pilani.ac.in/pilani/vaibhavdixit/profile
>>>>> https://www.linkedin.com/in/vaibhav-dixit-b1a07a39/
>>>>>
>>>>> ORCID ID: https://orcid.org/0000-0003-4015-2941
>>>>>
>>>>> http://scholar.google.co.in/citations?user=X876BKcAAAAJ&hl=en&oi=sra
>>>>>
>>>>> P Please consider the environment before printing this e-mail
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Received on Wed Oct 07 2020 - 16:30:02 PDT
