Please be also cautious about the fact that MMPBSA is not truly
decomposable (don't recall now a reference but we do provide one in our
paper). All in all, I'd say be careful about drawing any conclusions
from subtle differences in MMPBSA results in general ...
Vlad
On 05/18/2015 04:31 PM, Vlad Cojocaru wrote:
> My opinion is that the question is "how much you can trust the
> estimation of the average ?". For that, you need the standard error of
> uncorrelated data ...
>
> The fluctuation around the average will not give you any information
> as the MMPBSA (in my understanding at least) is a method to estimate
> average dGs (or ddGs or dddGs for that matter)
>
> Vlad
>
> On 05/18/2015 04:23 PM, James Starlight wrote:
>> the question: is it it principle reasonable to compare fluctuations of
>> the dG for the specified residue (based on its decomposition data) for
>> several systems (e.g one receptor VS 10 different ligands) to make
>> some suggestions about contribution of the specified residue to the
>> molecular phenotype (e.g will ligand act as agonist or antagonist)? I
>> just compare several such profiles (taken from the last column of the
>> COMPLEX array from the detailed decomposition logs) for the residue
>> which made one of the dominant contribution to the AVERAGED binding
>> energy for all of my systems and didn't seen big difference between
>> them besides big fluctuations in each case (e.g values ranges from -1
>> to +15 being around +5 on average).
>>
>> James
>>
>> 2015-05-18 16:16 GMT+02:00 James Starlight <jmsstarlight.gmail.com>:
>>> Thanks for help again, Vlad!
>>> However based on averaged values taken directly from standard
>>> decomposition output of that system: the energy value of this residue
>>> was around -1. So I suppose that in the detailed log the energy of
>>> this residue are also should fluctuate around this averaged shouldn't
>>> it ?
>>>
>>> Regards,
>>>
>>> J.
>>>
>>> 2015-05-18 15:53 GMT+02:00 Vlad Cojocaru
>>> <vlad.cojocaru.mpi-muenster.mpg.de>:
>>>> Sorry James, I did not use this output for decomposition analysis. I
>>>> only used it for the overall energy analysis during the
>>>> simulations. So,
>>>> I don't know exactly if I can advise you on this ...
>>>>
>>>> The fact that you have positive values does not say much. Depending on
>>>> the methodology you are using (MMPBSA allows lots of different
>>>> alternative protocols) the values might be positive or negative. It
>>>> may
>>>> be that you need to look at all residues and search for those with the
>>>> "least positive" contributions.
>>>>
>>>> We recently published a paper in Structure (by Felipe Merino et al
>>>> 2014)
>>>> in which we look at protein-DNA complexes. In that case we do get
>>>> negative values for those residues which contribute positively but as
>>>> soon as you change parameters and system, you may get all values
>>>> positive. The paper has a detailed MMPBSA protocol and discusses
>>>> some of
>>>> the parameters used .. it may be worth reading. We are also
>>>> preparing a
>>>> follow-up with more detailed data on the MMPBSA (but its just in the
>>>> making).
>>>>
>>>> Maybe somebody else may chime in here and help more than I can
>>>>
>>>> Best
>>>> Vlad
>>>>
>>>>
>>>>
>>>> On 05/18/2015 03:15 PM, James Starlight wrote:
>>>>> The question is only to what array from the decomposition log will be
>>>>> what I'm looking for e.g I'm interesting in the energy dynamics of
>>>>> the
>>>>> tyr- 234 residue of the receptor which have dominant contribution to
>>>>> the binding so its energy (enthalpy) must be very negative.
>>>>> In the first array which seems what I'm looking for I have only
>>>>> positive values in all snapshots:
>>>>> Complex:
>>>>>
>>>>> Total Energy Decomposition:
>>>>> Frame #,Residue,Internal,van der Waals,Electrostatic,Polar
>>>>> Solvation,Non-Polar Solv.,TOTAL
>>>>>
>>>>>
>>>>> 1,234,110.877,-14.568,-87.049,-1.716,0.0200304,7.5640304
>>>>> ..
>>>>>
>>>>> 7,234,104.367,-14.487,-84.611,-3.651,0.01458,1.63258
>>>>> ..
>>>>>
>>>>> 16,234,116.053,-12.17,-87.315,-1.051,0.0055872,15.5225872
>>>>>
>>>>>
>>>>> but in the last DELTAS array the values in the same positions are
>>>>> slightly negative
>>>>>
>>>>> DELTAS:
>>>>>
>>>>> DELTA,Total Energy Decomposition:
>>>>> Frame #,Residue,Location,Internal,van der Waals,Electrostatic,Polar
>>>>> Solvation,Non-Polar Solv.,TOTAL
>>>>>
>>>>> 1,TYR 234,R TYR 234,0.0,-1.0,-1.313,1.901,-0.1018944,-0.5138944
>>>>> ..
>>>>>
>>>>> 16,TYR 234,R TYR 234,0.0,-0.291,-0.037,0.455,-0.094788,0.032212
>>>>>
>>>>> ..
>>>>>
>>>>> 35,TYR 234,R TYR 234,0.0,-0.92,0.216,0.161,-0.1295496,-0.6725496
>>>>>
>>>>>
>>>>>
>>>>> also I have two rest arrays for the RECEPTOR and for the LIGAND. So
>>>>> which one will be useful for me?
>>>>>
>>>>>
>>>>> 2015-05-18 14:37 GMT+02:00 Vlad Cojocaru
>>>>> <vlad.cojocaru.mpi-muenster.mpg.de>:
>>>>>> Once you have those data in a file, you can use any scripting
>>>>>> language
>>>>>> (python, perl, tcl, awk) to sort it in any way you want ...
>>>>>>
>>>>>> Vlad
>>>>>>
>>>>>> On 05/18/2015 01:38 PM, James Starlight wrote:
>>>>>>> btw what I've found in the log produced by -deo is that all data
>>>>>>> has
>>>>>>> been sorted in accordance to the frame number
>>>>>>> i.e
>>>>>>>
>>>>>>> Total Energy Decomposition:
>>>>>>> Frame #,Residue,Internal,van der Waals,Electrostatic,Polar
>>>>>>> Solvation,Non-Polar Solv.,TOTAL
>>>>>>>
>>>>>>> What would be most trivial way to sort all of those data primarily
>>>>>>> based on the residue number ? In fact each time I'd like only to
>>>>>>> look
>>>>>>> on the dynamics (as the function of the frame number from 1st
>>>>>>> column)
>>>>>>> of the total energy (last column) of the one chosen residue (taken
>>>>>>> from the 2nd column).
>>>>>>>
>>>>>>> Thanks for any ideas!
>>>>>>>
>>>>>>> James
>>>>>>>
>>>>>>> 2015-05-15 13:30 GMT+02:00 James Starlight
>>>>>>> <jmsstarlight.gmail.com>:
>>>>>>>> Thanks so much, Vlad!
>>>>>>>> -eo and -deo flags seems like what I was looked for assuming
>>>>>>>> that I'd
>>>>>>>> like also to look into enthalpy fluctuations for specified
>>>>>>>> residues of
>>>>>>>> the decomposition output.
>>>>>>>>
>>>>>>>> Regards,
>>>>>>>>
>>>>>>>> James
>>>>>>>>
>>>>>>>> 2015-05-13 17:47 GMT+02:00 Vlad Cojocaru
>>>>>>>> <vlad.cojocaru.mpi-muenster.mpg.de>:
>>>>>>>>> If I understand your problem correctly, it can be solved
>>>>>>>>> simply by
>>>>>>>>> specifying an output file of your wish using the "-eo" option
>>>>>>>>> (page 632
>>>>>>>>> amber 15 manual) ... This will store all energy terms for all
>>>>>>>>> frames
>>>>>>>>> analyzed ... Did your try this ? Isn't it what you want ?
>>>>>>>>>
>>>>>>>>> Vlad
>>>>>>>>>
>>>>>>>>>
>>>>>>>>> On 05/13/2015 05:26 PM, James Starlight wrote:
>>>>>>>>>> So no new options (like specified values for verbose or
>>>>>>>>>> dec_verbose)
>>>>>>>>>> should not be added to the inputs? I really didn't find
>>>>>>>>>> information
>>>>>>>>>> about dumping of the outputs within the manual. Into which
>>>>>>>>>> file should
>>>>>>>>>> I look?
>>>>>>>>>>
>>>>>>>>>> Thanks!
>>>>>>>>>>
>>>>>>>>>> James
>>>>>>>>>>
>>>>>>>>>> 2015-05-13 16:04 GMT+02:00 Vlad Cojocaru
>>>>>>>>>> <vlad.cojocaru.mpi-muenster.mpg.de>:
>>>>>>>>>>> You can dump the output into a file using the "-eo" option (see
>>>>>>>>>>> MMPBSA.py part of the AMBER manual).
>>>>>>>>>>>
>>>>>>>>>>> Best
>>>>>>>>>>> Vlad
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>> On 05/13/2015 03:55 PM, James Starlight wrote:
>>>>>>>>>>>> Dear Amber users!
>>>>>>>>>>>>
>>>>>>>>>>>> Based on the mmgbsa outputs (including both dG and
>>>>>>>>>>>> decomposition
>>>>>>>>>>>> outputs) I'd like to monitor fluctuations of the total dG
>>>>>>>>>>>> over the
>>>>>>>>>>>> trajectory (and possible to see both dH and dS dynamics).
>>>>>>>>>>>> Also I'd
>>>>>>>>>>>> like to do the same on the per-residue basis (E.g to see
>>>>>>>>>>>> how dH
>>>>>>>>>>>> fluctuate for several chosen residues). I'd be thankful if
>>>>>>>>>>>> someone
>>>>>>>>>>>> provide me what flags should I activate in the mmgbsa input
>>>>>>>>>>>> file and
>>>>>>>>>>>> what output files will contain that information?
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>> Thanks!
>>>>>>>>>>>>
>>>>>>>>>>>> James
>>>>>>>>>>>>
>>>>>>>>>>>> _______________________________________________
>>>>>>>>>>>> AMBER mailing list
>>>>>>>>>>>> AMBER.ambermd.org
>>>>>>>>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>> --
>>>>>>>>>>> Dr. Vlad Cojocaru
>>>>>>>>>>> Computational Structural Biology Laboratory
>>>>>>>>>>> Department of Cell and Developmental Biology
>>>>>>>>>>> Max Planck Institute for Molecular Biomedicine
>>>>>>>>>>> Röntgenstrasse 20, 48149 Münster, Germany
>>>>>>>>>>> Tel: +49-251-70365-324; Fax: +49-251-70365-399
>>>>>>>>>>> Email: vlad.cojocaru[at]mpi-muenster.mpg.de
>>>>>>>>>>> http://www.mpi-muenster.mpg.de/43241/cojocaru
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>> _______________________________________________
>>>>>>>>>>> AMBER mailing list
>>>>>>>>>>> AMBER.ambermd.org
>>>>>>>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>>>>>> _______________________________________________
>>>>>>>>>> AMBER mailing list
>>>>>>>>>> AMBER.ambermd.org
>>>>>>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>>>>> --
>>>>>>>>> Dr. Vlad Cojocaru
>>>>>>>>> Computational Structural Biology Laboratory
>>>>>>>>> Department of Cell and Developmental Biology
>>>>>>>>> Max Planck Institute for Molecular Biomedicine
>>>>>>>>> Röntgenstrasse 20, 48149 Münster, Germany
>>>>>>>>> Tel: +49-251-70365-324; Fax: +49-251-70365-399
>>>>>>>>> Email: vlad.cojocaru[at]mpi-muenster.mpg.de
>>>>>>>>> http://www.mpi-muenster.mpg.de/43241/cojocaru
>>>>>>>>>
>>>>>>>>>
>>>>>>>>> _______________________________________________
>>>>>>>>> AMBER mailing list
>>>>>>>>> AMBER.ambermd.org
>>>>>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>>> _______________________________________________
>>>>>>> AMBER mailing list
>>>>>>> AMBER.ambermd.org
>>>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>> --
>>>>>> Dr. Vlad Cojocaru
>>>>>> Computational Structural Biology Laboratory
>>>>>> Department of Cell and Developmental Biology
>>>>>> Max Planck Institute for Molecular Biomedicine
>>>>>> Röntgenstrasse 20, 48149 Münster, Germany
>>>>>> Tel: +49-251-70365-324; Fax: +49-251-70365-399
>>>>>> Email: vlad.cojocaru[at]mpi-muenster.mpg.de
>>>>>> http://www.mpi-muenster.mpg.de/43241/cojocaru
>>>>>>
>>>>>>
>>>>>> _______________________________________________
>>>>>> AMBER mailing list
>>>>>> AMBER.ambermd.org
>>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>> _______________________________________________
>>>>> AMBER mailing list
>>>>> AMBER.ambermd.org
>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>> --
>>>> Dr. Vlad Cojocaru
>>>> Computational Structural Biology Laboratory
>>>> Department of Cell and Developmental Biology
>>>> Max Planck Institute for Molecular Biomedicine
>>>> Röntgenstrasse 20, 48149 Münster, Germany
>>>> Tel: +49-251-70365-324; Fax: +49-251-70365-399
>>>> Email: vlad.cojocaru[at]mpi-muenster.mpg.de
>>>> http://www.mpi-muenster.mpg.de/43241/cojocaru
>>>>
>>>>
>>>> _______________________________________________
>>>> AMBER mailing list
>>>> AMBER.ambermd.org
>>>> http://lists.ambermd.org/mailman/listinfo/amber
>> _______________________________________________
>> AMBER mailing list
>> AMBER.ambermd.org
>> http://lists.ambermd.org/mailman/listinfo/amber
>
--
Dr. Vlad Cojocaru
Computational Structural Biology Laboratory
Department of Cell and Developmental Biology
Max Planck Institute for Molecular Biomedicine
Röntgenstrasse 20, 48149 Münster, Germany
Tel: +49-251-70365-324; Fax: +49-251-70365-399
Email: vlad.cojocaru[at]mpi-muenster.mpg.de
http://www.mpi-muenster.mpg.de/43241/cojocaru
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Received on Mon May 18 2015 - 08:00:04 PDT
