Thank you very much for your answer.
The ring is from uridine hence no symmetric, indeed a flipping of the ring would require a temporary increase of the local rmsd which is not favourable due to the penalty on the energy, maybe explaining the local minimum.
I also tried performing the tMD starting from the final state of the first tMD applying a new tMD constraint just for the ligand, which did not work either.
For the dihedral restraint would you suggest to change nmropt=1 from the beginning?
> On 23 Feb 2016, at 13:19, Carlos Simmerling <carlos.simmerling.gmail.com> wrote:
>
> Maybe you need a dihedral restraint? A flipped ring isn't going to show up
> strongly in an entire protein rmsd. Is the ring symmetric? Depending on the
> details, the rmsd may go up as it flips, thus your current structure may be
> a local minimum.
> On Feb 23, 2016 6:26 AM, "Jean-Marc Billod" <jmbillod.cib.csic.es> wrote:
>
>> It is indeed what I want and I understand that the ligand isn’t
>> contributing a lot in the global rmsd average. Is there another way to
>> force the flipping of the ring?
>>
>>> On 23 Feb 2016, at 12:14, Carlos Simmerling <carlos.simmerling.gmail.com>
>> wrote:
>>>
>>> Your fit and rmsd mask are for all non water heavy atoms. Is that what
>> you
>>> want? If the ligand is a small part of the system it won't contribute
>> much
>>> to the average in the rmsd.
>>> On Feb 23, 2016 4:45 AM, "Jean-Marc Billod" <jmbillod.cib.csic.es>
>> wrote:
>>>
>>>> Dear all,
>>>>
>>>> I have performed tMD with AMBER12 using the following script:
>>>>
>>>> &cntrl
>>>> nstlim = 2500000, dt = 0.002,
>>>> ntx = 1, irest = 0,
>>>> ntpr = 500, ntwr = 500, ntwx = 500,
>>>> tempi = 300., temp0 = 300.,
>>>> cut = 15.0,
>>>> ntt = 1,
>>>> ntb = 2, ntp = 1,
>>>> ntc = 2, ntf = 2,
>>>> nscm = 0,
>>>> itgtmd = 1, tgtmdfrc = 0.25,
>>>> tgtrmsd = 4.9,
>>>> tgtfitmask="!.H= & !:WAT",
>>>> tgtrmsmask="!.H= & !:WAT",
>>>> nmropt=1,
>>>>
>>>> /
>>>> &wt
>>>> TYPE='TGTRMSD', istep1=1, istep2=400000,
>>>> value1 = 4.9, value2 = 4.2,
>>>> /
>>>> &wt
>>>> TYPE='TGTRMSD', istep1=400001, istep2=800000,
>>>> value1 = 4.2, value2 = 3.0,
>>>> /
>>>> &wt
>>>> TYPE='TGTRMSD', istep1=800001, istep2=1200000,
>>>> value1 = 3.000, value2 = 2.0,
>>>> /
>>>>
>>>> &wt
>>>> TYPE='TGTRMSD', istep1=1200001, istep2=1600000,
>>>> value1 = 2.000, value2 = 1.0,
>>>> /
>>>> &wt
>>>> TYPE='TGTRMSD', istep1=1600001, istep2=2000000,
>>>> value1 = 1.0, value2 = 0.0,
>>>> /
>>>> &wt
>>>> TYPE='TGTRMSD', istep1=2000000, istep2=2500000,
>>>> value1 = 0.0, value2 = 0.0,
>>>> /
>>>>
>>>> I used two crystal structures with the ligand inside the binding pocket;
>>>> in the final crystal, one aromatic ring of the ligand is flipped
>> compared
>>>> to the first crystal. I performed the simulation and I had no error but
>> I
>>>> realized that the ligand does not undergo the flipping... basically only
>>>> the conformation of the protein changes but not the one of the ligand.
>> In
>>>> fact, the last RMSD is not 0:
>>>>
>>>> R M S F L U C T U A T I O N S
>>>>
>>>>
>>>> NSTEP = 2500000 TIME(PS) = 5025.000 TEMP(K) = 0.88 PRESS =
>>>> 107.6
>>>> Etot = 238.4099 EKtot = 123.0485 EPtot =
>>>> 268.7670
>>>> BOND = 32.9511 ANGLE = 48.2236 DIHED =
>>>> 30.4487
>>>> 1-4 NB = 18.4036 1-4 EEL = 73.6341 VDWAALS =
>>>> 195.7646
>>>> EELEC = 272.2557 EHBOND = 0.0000 RESTRAINT =
>>>> 210.8199
>>>> EAMBER (non-restraint) = 57.9471
>>>> EKCMT = 94.1915 VIRIAL = 1587.6094 VOLUME =
>>>> 717.5546
>>>> Density =
>>>> 0.0011
>>>> Ewald error estimate: 0.4427E-04
>>>> Current RMSD from reference: 0.972
>>>> Current target RMSD: 0.000
>>>>
>>>>
>>>> Am I doing anything wrong? Any suggestions?
>>>>
>>>> Thanks a lot,
>>>> Jean-Marc
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Received on Tue Feb 23 2016 - 06:00:02 PST
