AMBER Archive (2006)

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

From: JunJun Liu (ljjlp03_at_gmail.com)
Date: Tue Jun 20 2006 - 18:45:52 CDT

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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