AMBER Archive (2006)

Subject: Re: AMBER: why has "ELE " a large fluctuation in MMP BSA?

From: Carlos Simmerling (carlos_at_csb.sunysb.edu)
Date: Tue Jun 20 2006 - 20:54:51 CDT

no, I do not think the explicit water is wrong.
 this is just the way it is- postprocessing
may give large fluctuations. it doesn't mean anything
is wrong...
good luck!

JunJun Liu wrote:

> Thanks a lot to Prof.Simmerling and Prof.Cheatham,
>
> I understand now. It may be a problem that caused by too many water
> molecules, which make a major energy contribution to the whole
> system. This is possible, because our simulated system contains
> 11,594 DNA+Protein+Ligand atoms v.s. 93,843 water atoms. If this is
> the case, can I say it's a disadvantage of explicit solvation model
> of MD, in which systems containing large amount of solvent molecules
> may possible not be treated correctly? Is it right?
>
> Thanks!
>
> On Tue, 20 Jun 2006 21:19:10 -0300, Carlos Simmerling
> <carlos_at_csb.sunysb.edu> wrote:
>
>> of course my suggestions are just ideas, it is entirely possible
>> that you have some error. what i meant was that your
>> observations are not that surprising.
>>
>> JunJun Liu wrote:
>>
>>> Dear Dr.Simmerling,
>>>
>>> Thanks a lot for the responses. I may not state the problem
>>> clearly. In this case, GB model is not used. What I did is like
>>> the followings:
>>> 1). MD simulation with explicit solvation box
>>> 2). extract snapshots from stable MD trajectory and remove waters
>>> and counterions
>>> 3). Perform 1 step(single point) gas phase minimization against
>>> those snapshots
>>>
>>> I know the energy from MD simulation contains solvent contribution,
>>> and this energy should be different with energy from gas phase.
>>> But it's abnormal that the gas-phase electrostatic energy
>>> fluctuate too much, which can be up to ~600kcal/mol. This is quite
>>> strange! We checked the RMSD of selected snapshots, the values are
>>> less than 0.3A, indicating the selected structures are very close!
>>> Any suggestions? Thanks!
>>>
>>> Regards!
>>>
>>> Liu
>>>
>>> On Tue, 20 Jun 2006 20:10:48 -0300, Carlos Simmerling
>>> <carlos_at_csb.sunysb.edu> wrote:
>>>
>>>> possible things to consider:
>>>>
>>>> 1) the GB solvated system is much smaller, so larger fluctuations
>>>> are expected (check
>>>> a stat mech book)
>>>> 2) you are calculating energies with a different energy function
>>>> than you used to
>>>> generate the simulation. It is entirely possible that the energy
>>>> fluctuations for the
>>>> trajectory from explicit water differ from what you would get if
>>>> you used structures
>>>> that were actually sampled in the GB model.
>>>> 3) the ele in the explicit water includes solvation, and the GB
>>>> one does not.
>>>> it is well known that these terms tend to fluctuate in the
>>>> opposite direction
>>>> so leaving the solvation energy out will give higher fluctuations.
>>>>
>>>>
>>>>
>>>> JunJun Liu wrote:
>>>>
>>>>> Hi all,
>>>>>
>>>>> It's acutally a sander related problem. The sander program
>>>>> produces a stable trajectory when performing a MD simulation in
>>>>> explicit water box, but gives out very unstable energy curve if
>>>>> doing vacuum single-point energy calculation against snapshots
>>>>> of this MD trajectory(with waters and counterions removed).
>>>>> What could be the reason? Since it's a DNA+Protein system, does
>>>>> this mean the force field(ff99) can't describe the system well?
>>>>> Or caused by other problem? Any suggestions? Thanks!
>>>>>
>>>>> Regards!
>>>>>
>>>>> Liu
>>>>>
>>>>> On Tue, 20 Jun 2006 10:47:44 -0300, yxiong99 <yxiong99_at_163.com>
>>>>> wrote:
>>>>>
>>>>>> Dear sir,
>>>>>> I have a strange problem when I did MM_PBSA. My system is
>>>>>> protein-DNA-ligand complex. The receptor is protein-DNA complex,
>>>>>> and the ligand is a small molecule. I get 50 points from a
>>>>>> stable 200 ps MD simulation. In that simulation, it is obvious
>>>>>> that energy for every step in 200ps simulation don't change so
>>>>>> much. However after I did MM_PBSA(I only did MM section to
>>>>>> test), I found "ELE " has a large fluctuation.
>>>>>> Could you please give me some suggestion on it?
>>>>>> MD results:
>>>>>> -------------------------------------------------------------------------------------
>>>>>> A V E R A G E S O V E R 100000 S T E P S
>>>>>>
>>>>>> NSTEP = 100000 TIME(PS) = 1200.000 TEMP(K) = 297.94
>>>>>> PRESS = 1.0
>>>>>> Etot = -1755294.9287 EKtot = 6319.6873 EPtot
>>>>>> = -1761614.6160
>>>>>> BOND = 1374.4608 ANGLE = 5579.4236 DIHED
>>>>>> = 2833.4301
>>>>>> 1-4 NB = 2212.7443 1-4 EEL = -5183.5817 VDWAALS
>>>>>> = -5710.5417
>>>>>> EELEC = -1762720.5514 EHBOND = 0.0000 RESTRAINT
>>>>>> = 0.0000
>>>>>> EKCMT = 1.9203 VIRIAL = -24.2883 VOLUME
>>>>>> = 1239972.2032
>>>>>> Density
>>>>>> = 0.8688
>>>>>> Ewald error estimate: 0.9679E+00
>>>>>> ------------------------------------------------------------------------------
>>>>>> R M S F L U C T U A T I O N S
>>>>>>
>>>>>> NSTEP = 100000 TIME(PS) = 1200.000 TEMP(K) = 2.04
>>>>>> PRESS = 51.9
>>>>>> Etot = 3.7961 EKtot = 43.3440 EPtot
>>>>>> = 45.1668
>>>>>> BOND = 29.6708 ANGLE = 45.6035 DIHED
>>>>>> = 26.7273
>>>>>> 1-4 NB = 13.7112 1-4 EEL = 38.6013 VDWAALS
>>>>>> = 35.0353
>>>>>> EELEC = 47.8923 EHBOND = 0.0000 RESTRAINT
>>>>>> = 0.0000
>>>>>> EKCMT = 0.9180 VIRIAL = 1390.4239 VOLUME
>>>>>> = 142.3465
>>>>>> Density
>>>>>> = 0.0001
>>>>>> Ewald error estimate: 0.2632E-04
>>>>>>
>>>>>> MMPBSA results:
>>>>>> -------------------------------------------------------------------------------------
>>>>>> # COMPLEX
>>>>>> RECEPTOR LIGAND
>>>>>> # ----------------------- -----------------------
>>>>>> -----------------------
>>>>>> # MEAN STD MEAN
>>>>>> STD MEAN STD
>>>>>> # ======================= =======================
>>>>>> =======================
>>>>>> ELE -23558.26 691.21 -23410.78
>>>>>> 683.97 61.30 0.02
>>>>>> VDW -2745.00 28.83 -2730.24
>>>>>> 29.06 16.89 0.01
>>>>>> INT 13160.44 52.99 13382.69
>>>>>> 54.40 54.10 0.04
>>>>>> GAS -13142.81 696.51 -12758.34
>>>>>> 689.12 132.29 0.03
>>>>>> # DELTA
>>>>>> # -----------------------
>>>>>> # MEAN STD
>>>>>> # =======================
>>>>>> ELE -208.78 64.66
>>>>>> VDW -31.64 3.68
>>>>>> INT -276.34 17.50
>>>>>> GAS -516.77 67.28
>>>>>>
>>>>>> 　　　　　　　　Ying Xiong
>>>>>> 　　　　　　　　yxiong99_at_163.com
>>>>>> 　　　　　　　　　　2006-06-19
>>>>>>
>>>>>
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