Hi Brian,
Thanks for the response. I am trying tempi = 100 & 150 and will let you
know the result.
Could you explain in more details about "how to carefully calculated or
canceled out byan appropriate thermodynamic cycle" to overcome the subtle
QMMM TI difficulties? If I follow and modify the protocol of amber TI
tutorial, <
http://ambermd.org/tutorials/advanced/tutorial9/> will I
overcome the subtle QMMM TI difficulty? Or there are something important
tips not mentioned in the tutorial?
When visualized the QMMM TI trajectory, I don't see weird points. The
ligand still binds to the protein active site with normal fluctuation; no
blow up. The following is the RMSD v.s. time plot of the 100 ps
production run in step 3, V0 group.
http://i1076.photobucket.com/albums/w454/happypsu4/RMSD.jpg
Here is my RMSD script
######################################
cat << EOF > AAA.calc_rms
trajin BBB.mdcrd
reference C.inpcrd
rms reference mass out AAA.rms .N,CA,C time 0.5
EOF
$AMBERHOME/bin/ptraj C.prmtop < AAA.calc_rms
###############################################
Please let me know if any comment.
Many thanks,
Henry
On Fri, Aug 3, 2012 at 1:44 PM, Brian Radak <radak004.umn.edu> wrote:
> Hi Henry,
>
> You appear to be running thermostatted MD (ntt != 1 and gamma_ln > 0), in
> which case energy shouldn't be conserved, especially when you set tempi =
> 0., as the system quickly converts potential energy into kinetic energy.
> You might consider speeding that up by setting tempi > 0 or using various
> heating protocols.
>
> As for QM/MM, I believe it is quite normal for the energy to jump as the QM
> code includes atomic heats of formation and therefore has a different zero
> of potential energy. This is a subtle difficulty in performing TI with
> QM/MM because the zero of energy will be an offset in any free energies
> that you compute and must either be carefully calculated or canceled out by
> an appropriate thermodynamic cycle.
>
> Are your dynamics unstable? Relatively large changes in energy during
> equilibration are not necessarily cause for concern unless you are getting
> vlimit or SHAKE errors.
>
> Regards,
> Brian
>
> On Fri, Aug 3, 2012 at 1:44 PM, Pin-Chih Su (Henry Su) <psu4.uic.edu>
> wrote:
>
> > Dear Amber,
> >
> > When I run a TI job, the energy doesn't seem to conserve in each
> clambda
> > step in no matter step 1, step 2 (soft core potential step) and step 3.
> > The total energy always drops significantly at the beginning of each
> stage
> > (minimization, constant volume equilibrium, constant
> > pressure equilibrium and production run). Moreover, when MD enters into a
> > QMMM production run, the total energy will drop again and then reach a
> > higher value than the total energy of minimization and equilibrium.
> Please
> > see the following Xmgrace figures for more details.
> >
> > *TI_energy<
> > http://i1076.photobucket.com/albums/w454/happypsu4/TI_energy.png>
> > (**http://i1076.photobucket.com/albums/w454/happypsu4/TI_energy.png**)*
> > *TI_pressure<
> > http://i1076.photobucket.com/albums/w454/happypsu4/TI_pressure.png>(
> > http://i1076.photobucket.com/albums/w454/happypsu4/TI_pressure.png)*
> > *TI_temperature<
> > http://i1076.photobucket.com/albums/w454/happypsu4/TI_temperature.png>(
> > http://i1076.photobucket.com/albums/w454/happypsu4/TI_temperature.png)*
> >
> >
> > The following is my Amber TI script in step 1 (to simplify, I just show
> > half of the script, as in a group ):
> >
> > mask0=':MAA.F14,CL17'
> > mask1=
> >
> > for X in 1,2,3
> >
> > do
> >
> > ###################### minimization step ################################
> >
> > imin = 1,
> > maxcyc = 2000,
> > ntmin = 2,
> > ntpr = 100,
> > ntf = 2,
> > ntc = 1, (I also tried ntc=2 here)
> > ntb = 1,
> > cut = 10.0,
> > icfe = 1,
> > clambda = 0.${X},
> > ifsc=0,
> > crgmask='${mask0}',
> > &end
> > ###########################Constant volume equilibrium to equilibrate
> > temperature ######################################
> >
> > imin = 0,
> > irest = 0,
> > ntx = 1,
> > ntb = 1,
> > cut = 10.0,
> > ntr = 1,
> > ntc = 2,
> > ntf = 2,
> > tempi = 0.0,
> > temp0 = 300.0,
> > ntt = 3,
> > gamma_ln = 2.0,
> > nstlim = 50000,
> > dt = 0.001,
> > ntpr = 250,
> > ntwx = 250,
> > ntwr = 2500,
> > icfe = 1,
> > clambda = 0.${X},
> > ifsc=0,
> > crgmask='${mask0}',
> > /
> > Keep the Protein fixed with weak restraints
> > 10.0
> > RES 1 258
> > /
> >
> > END
> >
> > ##################################### Constant Pressure equilibrium to
> get
> > a proper density #########################
> > imin = 0,
> > irest = 1,
> > ntx = 7,
> > ntb = 2,
> > pres0 = 1.0,
> > ntp = 1,
> > taup = 2.0,
> > cut = 10,
> > ntr = 0,
> > ntc = 2,
> > ntf = 2,
> > tempi = 300.0,
> > temp0 = 300.0,
> > ntt = 3,
> > gamma_ln = 2.0,
> > nstlim = 50000,
> > dt = 0.001
> > ntpr = 250,
> > ntwx = 250,
> > ntwr = 2500,
> > icfe = 1,
> > clambda = 0.${X},
> > ifsc=0,
> > crgmask='${mask0}',
> > &end
> > ############################QMMM production
> > run###############################################
> > imin = 0,
> > ntx = 5,
> > irest = 1,
> > ntb = 2,
> > ntp = 1,
> > pres0 = 1.0,
> > taup = 2.0,
> > ntf = 1,
> > ntc = 1,
> > cut = 10.0,
> > temp0 = 300.0,
> > ntt = 3,
> > gamma_ln = 2.0,
> > nstlim = 50000,
> > dt = 0.001,
> > ntpr = 250,
> > ntwr = 2500,
> > ntwx = 250,
> > icfe=1,
> > clambda = 0.${X},
> > ifsc=0,
> > crgmask='${mask0}',
> > ifqnt = 1
> > /
> > &qmmm
> > iqmatoms= 3868,3869,3870,3871,3872,
> > 3873,3874,3875,3876,3877,
> > 3878,3879,3880,3881,3882,
> > 3883,3884,3885,3886,3887,
> > 3888,3889,3890,1395,1394,
> > 1396,1398,1399,2328,2327,
> > 3833,3834,3835,3836,3837,
> > 3838,3839,3840,3841,3862,
> > 3863,3864,3865,3866,3867,
> > qmchage=-1,
> > qm_theory='PM3',
> > qmshake=0,
> > qm_ewald=1,
> > qm_pme=1,
> > /
> > &end
> >
> >
> >
> ############################################################################
> >
> > I have tried
> >
> > a. turn off QMMM. Or keep QMMM but with qmshake=1,. The same issue
> > b. Run in both Amber 11 & 12, The same issue
> > c. Turn on / off SHAKE. The same issue.
> > d. Turn off Langevin Dynamic. The same issue
> > e. Switch to Andersen temperature control. The same issue.
> > f. Prepare new .prmtop and .inpcrd files and run again. The same issue
> > g. I have set ntpr=1 and check all the .out files by "gvim -d" and total
> > energies, temperature, pressure and all the MM components are the same in
> > the same group file.
> > h. The restart files from V0 to V1 are identical.
> >
> > I only tried 9 windows so far.
> > clambda = 0.${X}, for X in 1 2 3 4 5 6 7 8 9
> > But I guess number of windows is not the issue here.
> >
> > Please let me know if any comment. Many comments.
> >
> > Henry
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
>
>
>
> --
> ================================ Current Address =======================
> Brian Radak : BioMaPS
> Institute for Quantitative Biology
> PhD candidate - York Research Group : Rutgers, The State
> University of New Jersey
> University of Minnesota - Twin Cities : Center for Integrative
> Proteomics Room 308
> Graduate Program in Chemical Physics : 174 Frelinghuysen Road,
> Department of Chemistry : Piscataway, NJ
> 08854-8066
> radak004.umn.edu :
> radakb.biomaps.rutgers.edu
> ====================================================================
> Sorry for the multiple e-mail addresses, just use the institute appropriate
> address.
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
Pin-Chih Su (Henry Su)
Graduate Student
Center for Pharmaceutical Biotechnology (MC 870)
College of Pharmacy, University of Illinois at Chicago
900 South Ashland Avenue, Room 1052
Chicago, IL 60607-7173
office 312-996-5388
fax 312-413-9303
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Received on Mon Aug 06 2012 - 16:00:02 PDT
