Re: [AMBER] Issues with Umbrella Sampling Simulations involving lipid bilayer

From: Casalini Tommaso <tommaso.casalini.chem.ethz.ch>
Date: Fri, 17 Jan 2020 09:24:23 +0000

Dear Stephan,

right now the restraint is aimed at keeping the polymer COM/bilayer COM distance at 0 (as shown but the input file that I copied).

I started by simply placing the chain in the simulation box, after equilibration the distance was about 4 nm.

The output file with the distances was correctly written, but the restraint energy was still ****** and the restraint was ineffective (the chain was not moving in the center).

I thought that the distance was too high so I tried to keep the distance equal to 3 nm, but the issue remained.

Then I rebuilt the system by placing at the beginning the polymer in the middle of the bilayer (distance equal to about 0).

Right now the restraint energy should be reasonable, but it is still *******.

The output file with the distances is correctly written, the distance is equal to about 0.

If necessary, I can share my files to check if someone can reproduce my issue.

________________________________
Da: Stephan Schott <schottve.hhu.de>
Inviato: giovedý 16 gennaio 2020 23:37:43
A: AMBER Mailing List
Oggetto: Re: [AMBER] Issues with Umbrella Sampling Simulations involving lipid bilayer

So it starts with ****? What is your initial distance then and what values
do you get in the dump file?

El jue., 16 ene. 2020 a las 13:39, Casalini Tommaso (<
tommaso.casalini.chem.ethz.ch>) escribiˇ:

> Dear Stephan,
>
> thanks a lot for your reply.
>
> I am using the pmemd.cuda module of AMBER16, without additional patches.
>
> I tried to implement your suggestion and the RESTRAINT energy goes crazy
> immediately, from step 1 (I put ntpr = 1).
>
> As mentioned in the previous mail, what puzzles me is that I used the same
> approach using a different membrane (pure DOPC) and everything went well.
>
> Best,
>
> Tommaso
>
>
> ________________________________
> Da: Stephan Schott <schottve.hhu.de>
> Inviato: giovedý 16 gennaio 2020 13:13:59
> A: AMBER Mailing List
> Oggetto: Re: [AMBER] Issues with Umbrella Sampling Simulations involving
> lipid bilayer
>
> Hi Tommaso,
> Are you using sander, pmemd or pmemd.cuda? What AMBER version are you
> using, and which patches have been applied? I remember there was an issue
> with COM restraints, fixed in update 13 of AMBER 18. You could try
> increasing the rate at which you save the trajectory frames, to take a look
> at the moment when the RESTRAINT energy goes crazy.
> Cheers,
>
> El jue., 16 ene. 2020 a las 10:32, Casalini Tommaso (<
> tommaso.casalini.chem.ethz.ch>) escribiˇ:
>
> > Dear Amber users and developers,
> >
> > I am performing Umbrella Sampling simulations to study the permeation of
> a
> > small polymer fragment inside a POPC/CHL 2:1 lipid bilayer.
> >
> >
> > I built the lipid bilayer with the CHARMM GUI website and I have obtained
> > an equilibrated structure, that I checked with the area per lipid and
> > bilayer thickness as a function of simulation time.
> >
> > I have subsequently put the polymer fragment in the simulation box and I
> > have rebuilt the simulation box with the AddToBox utility, adding water
> and
> > ions only along z.
> >
> > I ran additional simulations to obtain an equilibrated system
> > configuration and I started US simulations.
> >
> > I use the following input file:
> >
> >
> > Equil
> > &cntrl
> > imin = 0,
> > irest = 1,
> > ntx = 7,
> > ntb = 2,
> > pres0 = 1.0,
> > ntp = 3,
> > taup = 2.0,
> > cut = 10.0,
> > ntc = 2,
> > ntf = 2,
> > temp0 = 310.0,
> > tempi = 310.0,
> > ntt = 3,
> > gamma_ln = 1.0,
> > nstlim = 20000000,
> > dt = 0.002,
> > ntpr = 10000,
> > ntwx = 10000,
> > ntwr = 10000,
> > nmropt = 1,
> > csurften = 3,
> > gamma_ten = 0.0,
> > ninterface = 2,
> > tol = 0.0000001
> > /
> > &wt type = 'DUMPFREQ', istep1 = 100 /
> > &wt type = 'END', /
> > DISANG = ref_COM.rst
> > DUMPAVE = Pull_dist.dat
> > LISTIN = POUT
> > LISTOUT = POUT
> > /
> > /
> > &ewald
> > skinnb = 3.0,
> > /
> >
> > This is the ref_COM.rst file:
> >
> >
> > &rst
> > iat=-1,-1,
> > r1=-99.0,
> > r2=0.0,
> > r3=0.0,
> > r4=99.0,
> > rk2=2.5,
> > rk3=2.5,
> > iresid=0,
> > fxyz=0,0,1,
> > outxyz=1,
> >
> >
> igr1=1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,
> >
> >
> igr2=130,264,398,606,888,1022,1156,1364,1498,1632,1766,1900,2034,2168,2376,2510,2866,3000,3208,3342,3476,3610,3744,3878,4086,4294,4576,4710,4844,4978,5112,5320,5602,5736,6018,6226,6360,6568,6850,6984,7192,7326,7534,7668,7802,7936,8144,82
> >
> >
> 78,8412,8546,8754,8888,9022,9230,9512,9646,9780,9914,10048,10182,10316,10524,10954,11088,11222,11356,11490,11624,11758,11966,12248,12382,12516,12650,12858,12992,13126,13260,13468,13676,13884,14018,14226,14434,14568,14702,14836,14970,1510
> >
> >
> 4,15238,15520,15654,15862,15996,16204,16338,16472,16606,16740,17022,17156,17438,17572,17780,17914,18270,18552,18686,18820,18954,19088,19296,19430,19786,19920,20054,20188,20322,20456,20590,20724,20858,20992,21200,
> > /
> >
> > where atoms 1-63 belong to my polymer fragment, while atoms of igr2 are
> > the N31 atoms of the polar heads (I essentially follow the approach
> > explained by Dr. Dickson Callum in his tutorial). I checked the numbers
> and
> > they are correct.
> >
> > For some unknown reasons, I obtained this:
> >
> >
> > NSTEP = 10000 TIME(PS) = 10540.000 TEMP(K) = 309.33 PRESS =
> > -116.3
> > Etot = ************** EKtot = 34089.0039 EPtot =
> > **************
> > BOND = 2925.3688 ANGLE = 12094.6034 DIHED =
> > 7501.6413
> > 1-4 NB = 2919.0577 1-4 EEL = -42192.4792 VDWAALS =
> > 5238.4991
> > EELEC = -110714.2666 EHBOND = 0.0000 RESTRAINT =
> > **************
> > EAMBER (non-restraint) = -122227.5755
> > EKCMT = 9433.8540 VIRIAL = 10678.6782 VOLUME =
> > 495566.9126
> > SURFTEN =
> > -52.4235
> > Density =
> > 1.0067
> >
> >
> ------------------------------------------------------------------------------
> >
> > NMR restraints: Bond =********* Angle = 0.000 Torsion =
> 0.000
> >
> >
> ===============================================================================
> >
> > NSTEP = 20000 TIME(PS) = 10560.000 TEMP(K) = 311.67 PRESS =
> > 187.4
> > Etot = ************** EKtot = 34346.3750 EPtot =
> > **************
> > BOND = 2985.2622 ANGLE = 12157.1242 DIHED =
> > 7567.3432
> > 1-4 NB = 2901.6475 1-4 EEL = -42177.9928 VDWAALS =
> > 5504.9903
> > EELEC = -110692.8191 EHBOND = 0.0000 RESTRAINT =
> > **************
> > EAMBER (non-restraint) = -121754.4445
> > EKCMT = 9541.5155 VIRIAL = 7537.2160 VOLUME =
> > 495324.5851
> > SURFTEN =
> > 86.8556
> > Density =
> > 1.0072
> >
> >
> ------------------------------------------------------------------------------
> >
> > NMR restraints: Bond =********* Angle = 0.000 Torsion =
> 0.000
> >
> >
> ===============================================================================
> >
> > NSTEP = 30000 TIME(PS) = 10580.000 TEMP(K) = 307.85 PRESS =
> > -10.4
> > Etot = ************** EKtot = 33925.5469 EPtot =
> > **************
> > BOND = 3003.1912 ANGLE = 12038.2158 DIHED =
> > 7478.7713
> > 1-4 NB = 2874.2811 1-4 EEL = -42133.3378 VDWAALS =
> > 5436.8241
> > EELEC = -110538.2867 EHBOND = 0.0000 RESTRAINT =
> > **************
> > EAMBER (non-restraint) = -121840.3409
> > EKCMT = 9409.4898 VIRIAL = 9520.6799 VOLUME =
> > 495200.1274
> > SURFTEN =
> > -193.4285
> > Density =
> > 1.0075
> >
> >
> ------------------------------------------------------------------------------
> >
> > NMR restraints: Bond =********* Angle = 0.000 Torsion =
> 0.000
> >
> > If I do not add a restraint, the system behaves nicely.
> >
> > What puzzles me is that I used the same protocol and approach for the
> same
> > polymer fragment in a pure DOPC membrane and I had no problems, and the
> > obtained results are consistent.
> >
> > Can you provide some suggestions?
> >
> > I thank you in advance for your support!
> >
> > Tommaso
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
>
>
> --
> Stephan Schott Verdugo
> Biochemist
>
> Heinrich-Heine-Universitaet Duesseldorf
> Institut fuer Pharm. und Med. Chemie
> Universitaetsstr. 1
> 40225 Duesseldorf
> Germany
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>


--
Stephan Schott Verdugo
Biochemist
Heinrich-Heine-Universitaet Duesseldorf
Institut fuer Pharm. und Med. Chemie
Universitaetsstr. 1
40225 Duesseldorf
Germany
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Received on Fri Jan 17 2020 - 01:30:02 PST
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