Hi Prokopios,
Based on the reported large difference between the MD and TI energies, your input topology and/or coordinate files might be problematic. I can take a quick look if you don't mind giving me your input files.
Best,
Taisung
On Mon, Jul 24, 2023 at 12:27 PM Prokopios Andrikopoulos via AMBER < amber.ambermd.org> wrote:
> Dear AMBER Users,
> I've been trying to do a TI for a mutation (res position 362) on a
> quite large trimer (1125 res per chain with a ligand at each chain at
> positions
> 3376-3378 - the ligand associated to the mutation is at 3378). I'm
> using ff14sb with TIP3P via the Amber 22 pmemd.cuda and the parmed
> from Amber 18
> (v22 parmed does not work on my cluster installation atm). I've
> adapted the relaxation regime from tutorial 3.1, by changing ntmin=2,
> ntf=1 and ntp=1 to make it acceptable for TI. I do a minimization >
> slow heating > and a series of 1ns constant pressure runs (with one
> more minimization
> in-between) releasing slowly the restrains as in tutorial 3.1. The
> relaxation regime works without any problems without the TI keywords
> (icfe, clambda etc.) on the normal prmtop using either a box or
> truncated octahedron for solvation. When I prepare the dual topology
> parm+rst7 is where the problems start. My parmed command is: tiMerge
> :1-3377 :3378-6754
> :362 :3739. Parmed moves the mutated res in the merged files right
> after the 1st chain, so in the relaxation inputs I have to point to
> 1126 instead, with the associated ligand at 3379.
>
> While the normal relaxation w/out TI reports a normal Density of
> ~1.00, the TI calculations density is reported in the 0.12-0.25 range
> in the constant pressure runs. A difference in energy is also evident
> in the initial minimization between the normal system and the TI
> complex with λ =
> 0.0: i.e. after 1000 min steps, this is EAMBER = -2180402.3012 and
> -2171818.4624 for the normal and TI calculation, respectively.
> Below are inputs for the complex with λ = 0.0. The input for the
> constant pressure run is the 4th in the regime with reduced backbone
> restrains. This fails for all λ values at 65-%75% of the total steps with the ERROR:
> Calculation halted. Periodic box dimensions have changed too much
> from their initial values. I would appreciate any help with this
> problem, and I can provide more details for the calculations.
>
> A secondary problem I have encountered is when I use a truncated
> octahedron for the solvation of the system with solvateOct. I use this
> command in leap for the complex and the protein: setBox
> protein/complex vdw { x = y = z }, and then I manually edit the last
> line of
> protein/complex.rst7 and merged_protein/complex.rst7 with the angles a
> = b = c = 109.47. When I run the calculation, it halts with Error:
> ifbox=2 in prmtop but angles are not correct. Incidentally, when I set
> ifbox=3 it runs without this error. Is this an acceptable solution?
>
> minimisation
> &cntrl
> imin = 1, ntmin = 2, maxcyc = 10000,
> ntpr = 50, ntwe = 0, ntwr = 500,
> ntb = 1, ntp = 0, ntf = 1, ntc = 2,
> ntx = 1, ntr = 1, ioutfm = 1, ntxo = 2,
> cut = 10.0,
> restraintmask = ':1-3379',
> restraint_wt = 100.,
>
>
> icfe = 1, ifsc = 1, clambda = 0.0, scalpha = 0.5, scbeta = 12.0,
> logdvdl = 0,
> timask1 = ':362', timask2 = ':1126',
> scmask1 = ':362', scmask2 = ':1126', /
>
> &ewald
> /
>
>
> heating to 298K
> &cntrl
> imin = 0, nstlim = 1000000, irest = 0, ntx = 1, dt = 0.001,
> ntt = 3, temp0 = 298.0, tempi = 100.0, tautp = 1.0, ig = -1,
> ntc = 2, ntf = 1,
> ntb = 1, ntp = 0, tol = 0.00001,
> ioutfm = 1, iwrap = 0, ntxo = 2, nscm = 0, cut = 8.0,
> ntwe = 0, ntwx = 10000, ntpr = 1000, ntwr = 1000,
>
> nmropt = 1, gamma_ln = 1.,
> ntr = 1, restraint_wt = 100.,
> restraintmask=':1-3379',
>
> icfe = 1, ifsc = 1, clambda = 0.0, scalpha = 0.5, scbeta = 12.0,
> logdvdl = 0,
> timask1 = ':362', timask2 = ':1126',
> scmask1 = ':362', scmask2 = ':1126', /
>
> &ewald
> /
>
> &wt
> type='TEMP0',
> istep1 = 0, istep2 = 1000000,
> value1 = 100., value2 = 298.
> /
>
> &wt type = 'END'
> /
>
> 4th constant pressure run of 1ns
> &cntrl
> imin = 0, nstlim = 1000000, dt = 0.001,
> irest = 1, ntx = 5, ig = -1,
> temp0 = 298.0,
> ntc = 2, ntf = 1,
> ntwx = 10000, ntwe = 0, ntwr = 1000, ntpr = 1000,
> cut = 8.0, iwrap = 0,
> ntt = 3, gamma_ln = 1.0, ntb = 2, ntp = 1, barostat = 2,
> nscm = 0,
> ntr = 1, restraintmask = "@CA,N,C", restraint_wt = 1.
> ioutfm = 1, ntxo = 2,
>
> icfe = 1, ifsc = 1, clambda = 0.0, scalpha = 0.5, scbeta = 12.0,
> logdvdl = 0,
> timask1 = ':362', timask2 = ':1126',
> scmask1 = ':362', scmask2 = ':1126', /
>
> &ewald
> /
>
>
> Thanks for any suggestions
> P. A.
>
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Received on Mon Jul 24 2023 - 12:00:02 PDT
