Yup, the distorsion appears in all snapshots.. but as said.. I do not
see it in VMD (which is strange!), whereas I see it in Sirius..
the carbon is far away and no double numbering.. its the only one called
C14 in the "receptor".. eventually I would expect to see this problem
with the complex (where the inhibitor is also present with a C14, but
the prmtops are separated and the coordinates are not assigned by atom
names.. at least they shouldn't, right :s).
BOX NO
NTOTAL 4503
NSTART 1500
NSTOP 6500
NFREQ 50
NUMBER_LIG_GROUPS 1
LSTART 4474
LSTOP 4503
NUMBER_REC_GROUPS 1
RSTART 1
RSTOP 4473
This is my makecrd section.. so no double numbering.
And here follows the receptor %FORMAT section
%FORMAT(10I8)
4473 14 2246 2272 5088 3092 9168 6807
0 0
24677 285 2272 3092 6807 58 134 56
36 0
0 0 0 0 0 0 0 0
74 0
0
as well as of the complex section
%FORMAT(10I8)
4503 17 2257 2293 5108 3121 9563 7159
0 0
24820 286 2293 3121 7159 68 149 71
45 0
0 0 0 0 0 0 0 0
74 0
0
and the ligand section
%FORMAT(10I8)
30 7 11 21 20 29 44 43
0 0
143 1 21 29 43 10 15 7
9 0
0 0 0 0 0 0 0 0
30 0
0
However, many thanks for your suggestions.. I will try Ray's suggestion
to verify the MMPBSA results with excel.. I'll see.
Matthias
Bill Miller III ha scritto:
> If a carbon atom from the cofactor is far away from where it should be, this
> would certainly explain the strange numbers that you are getting with the
> internal energies. Are you seeing this distortion for all of the snapshots
> generated by mm_pbsa.pl, or is it just one snapshot? Does it's location in
> space correspond to a different atom in the complex coordinate files, or is
> the atom far away from the rest of the system? You might want to double
> check the numbers that you provided in the input file in the MAKECRD
> section.
>
> Good luck!
>
> -Bill
>
> On Thu, May 6, 2010 at 4:11 PM, Matthias Negri
> <m.negri.mx.uni-saarland.de>wrote:
>
>
>> Hi Ray,
>> no I am following a single trajectory approach.. this is why my results
>> sounds so confusing to me.
>>
>> However, I calculated the surface area for some snapshots and the average
>> value is about 950 A^2, thus a congruent value.
>>
>> Interestingly, when I visualize prmtop and coordinate of the "receptor"
>> (protein and cofactor) with VMD the structure looks fine, no distorted
>> bonds, correct lengths, etc. Otherwise, when I visualize prmtop and
>> coordinate with Sirius, a carbon atom of the cofactor seems to be far away.
>> This does not happen for the complex.
>>
>> What can the reason be for it? Might this be related with the strange
>> values emerged from the MM-PBSA calculation?
>>
>> Best regards,
>>
>> Matthias
>>
>>
>> Ray Luo, Ph.D. ha scritto:
>>
>>
>>> Matthias,
>>>
>>> Here are my observations of your numbers and related thoughts:
>>>
>>> 1) It seems that you are using the multiple trajectory approach, i.e. one
>>> separate trajectory for each of complex, receptor, and ligand? Otherwise,
>>> I
>>> don't understand the large INT energy in the Delta G part ...
>>>
>>> 2) The ELE energy, i.e. gas-phase Coulombic energy, and the PBELE energy
>>> are
>>> both small and almost cancel out each other. This is an indication that
>>> the
>>> electrostatic component seems to behave reasonably well in the
>>> calculation.
>>>
>>> 3) The PBSUR energy of -5 kcal/mol indicats a surface burial of 1000 A^2
>>> upon binding if you are using a surface tension of 5 cal/mol-A^2. This
>>> seems
>>> to be consistent with the very negative VDW energy upon binding. Can you
>>> rationalize the number for the surface burial upon binding, i.e. by doing
>>> a
>>> VMD visualization or some independent surface area calculation for a
>>> single
>>> snapshot to see whether the order of magnitude is correct?
>>>
>>> Good luck!
>>> Ray
>>>
>>> On Wed, May 5, 2010 at 4:45 PM, Matthias Negri
>>> <m.negri.mx.uni-saarland.de>wrote:
>>>
>>>
>>>
>>>
>>>> Hi,
>>>> many thanks for the suggestion. I will check again the charges of my
>>>> system
>>>> as well as the protonation states. In fact the "receptor" includes as
>>>> cofactor NADPH, which has a net charge of -4, mostly delocalized on the
>>>> phosphote oxygens.
>>>>
>>>> Again, thanks for the hint
>>>>
>>>> Matthias
>>>>
>>>> Dwight McGee ha scritto:
>>>>
>>>> Hi,
>>>>
>>>>
>>>>
>>>>> In my experiences I have only seen cases where the DELTA G was very
>>>>> high
>>>>> when certain things such as the ligand or residues from the receptor
>>>>> which
>>>>> interact w/ the ligand were not protonated correctly. As a suggestion I
>>>>> would make absolutely certain that everything has the correct charge.
>>>>> Good
>>>>> luck
>>>>>
>>>>> On Wed, May 5, 2010 at 6:17 AM, Matthias Negri
>>>>> <m.negri.mx.uni-saarland.de>wrote:
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>> Hello to everyone,
>>>>>> I'm experiencing some problems in an MM-PBSA calculation. My system
>>>>>> consists of enzyme, cofactor (NADPH) and inhibitor. Previous
>>>>>> calculations
>>>>>> (on different enzyme conformers) run fine, while for this specific case
>>>>>> the
>>>>>> final delta PBTOT I obtained is way to large (-324.94), mostly due to
>>>>>> an
>>>>>> imbalanced delta GAS (-356.32; in particular my delta INT is -120.87
>>>>>> and
>>>>>> delta VdW is -216.83). The topology files and the crd of complex,
>>>>>> receptor
>>>>>> and ligand look nice when I visualize them in VMD), no bonds are
>>>>>> distorted
>>>>>> or broken, etc.
>>>>>>
>>>>>> Hereafter my output file of the MM-PBSA calculation:
>>>>>>
>>>>>> # COMPLEX RECEPTOR
>>>>>> LIGAND
>>>>>> # ----------------------- -----------------------
>>>>>> -----------------------
>>>>>> # MEAN STD MEAN STD MEAN
>>>>>> STD
>>>>>> # ======================= =======================
>>>>>> =======================
>>>>>> ELE -7236.85 96.82 -7192.48 96.10 -25.76
>>>>>> 0.48
>>>>>> VDW -1199.12 28.96 -993.70 30.53 11.41
>>>>>> 1.22
>>>>>> INT 5792.37 46.59 5882.25 51.16 30.99
>>>>>> 3.65
>>>>>> GAS -2643.60 103.44 -2303.93 106.04 16.64
>>>>>> 3.53
>>>>>> PBSUR 104.29 1.24 105.77 1.26 3.44
>>>>>> 0.02
>>>>>> PBCAL -3415.05 88.12 -3424.16 88.17 -27.19
>>>>>> 0.51
>>>>>> PBSOL -3310.76 87.43 -3318.39 87.45 -23.75
>>>>>> 0.51
>>>>>> PBELE -10651.91 32.14 -10616.63 32.91 -52.95
>>>>>> 0.58
>>>>>> PBTOT -5954.37 44.68 -5622.32 51.50 -7.11
>>>>>> 3.48
>>>>>>
>>>>>> # DELTA # -----------------------
>>>>>> # MEAN STD
>>>>>> # =======================
>>>>>> ELE -18.62 6.32
>>>>>> VDW -216.83 5.70
>>>>>> INT -120.87 16.97
>>>>>> GAS -356.32 17.62
>>>>>> PBSUR -4.92 0.17
>>>>>> PBCAL 36.30 4.20
>>>>>> PBSOL 31.38 4.23
>>>>>> PBELE 17.68 5.12
>>>>>> PBTOT -324.94 17.04
>>>>>>
>>>>>> What can the reason for such huge energy differences be? Where should I
>>>>>> search for the mistake (If any is in)?
>>>>>>
>>>>>> Attached you can find input, output for the mm-pbsa calculation, as
>>>>>> well
>>>>>> as
>>>>>> prmtop and crd of ligand, "receptor (protein and cofactor)" and
>>>>>> complex.
>>>>>>
>>>>>> Many thanks,
>>>>>>
>>>>>> Matthias Negri
>>>>>>
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>>>>>>
>>>>>
>>>>>
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Received on Thu May 06 2010 - 15:30:03 PDT
