Dear Amber Experts,
I have a question regarding TI softcore perturbations. We more or less do what is described in the A9 TI softcore tutorial written by Thomas Steinbrecher and updated by Hannes Loeffler - perturbation of a side chain to obtain relative complexation free energies, using pmemd.cuda, with vdW and electrostatics softcore, vdW and charge perturbation in one step, bound and free. (By the way, ambermd.org seems not to be available at the moment.)
We have observed the following problem for a while (since Amber 22, I think):
The problem is, with Amber 24 (and Amber 22) the heating step of some or all lambda windows fails with some energies and/or T being NaN or ************** (see below for examples).
I have played around with many modifications of the input, on several GPUs, also with CPU only, using the 3-step or the 1-step protocol, but the problem remains. I also can't see any clashes or other problems when looking at the structures with VMD.
Sometimes submitting again helps for at least a few lambda windows, sometimes not.
Now the interesting thing: The same input works perfectly with Amber 20 (and Amber18, I remember). As long as I have Amber 20 available on our clusters, I can do the heating with this version, but I assume this version will not be available infinitely.
I would be happy to share input, prmtop, crd etc. off-list if one of the developers would like to reproduce this problem.
Any help would be very much appreciated!
Many thanks and best wishes,
Frank
heat.in:
restr on DNA, const vol, 200 ps heat-up,
langevin dyn, write en output every 1 ps,
write out rst and trj every 10 ps
&cntrl
imin = 0, nstlim = 200000, irest = 0, ntx = 1, dt = 0.001,
ntt = 3, temp0 = 298.0, gamma_ln = 2.0, ig = -1,
tempi = 0.0,
ntc = 2, ntf = 1,
ntb = 1,
cut = 10.0,
ioutfm = 1, iwrap = 1,
ntwe = 1000, ntwx = 10000, ntpr = 10000, ntwr = 10000,
noshakemask = ':8,11',
tishake = 1,
ntr = 1, restraint_wt = 5.00,
restraintmask='!:WAT & !.H=',
icfe = 1, ifsc = 1, clambda = 0.00, scalpha = 0.5, scbeta = 12.0,
logdvdl = 0,
timask1 = ':8', timask2 = ':11',
scmask1 = ':8.C16,O15,H22', scmask2 = ':11.C16,H22,H23,H24',
nmropt = 1, pencut=-0.001,
/
&wt type='REST', istep1=0,istep2= 200000,value1=1.0,
value2=1.0, /
&wt type='END' /
LISTIN=POUT
LISTOUT=POUT
DISANG=DNAtermini_ti.RST
Amber 24 p02
Tesla A 40
heat.out:
--------------------------------------------------------------------------------
4. RESULTS
--------------------------------------------------------------------------------
DOF for the SC part 1 of the system: 9
DOF for the SC part 2 of the system: 12
| TI region 1
NSTEP = 0 TIME(PS) = 0.000 TEMP(K) = 0.00 PRESS = 0.0
Etot = -106290.2119 EKtot = 0.0000 EPtot = -106290.2119
BOND = 10916.9779 ANGLE = 122.0025 DIHED = 403.4883
1-4 NB = 153.0514 1-4 EEL = -3075.5267 VDWAALS = 20127.5335
EELEC = -134937.7969 EHBOND = 0.0000 RESTRAINT = 0.0582
EAMBER (non-restraint) = -106290.2700
DV/DL = 139.0082
------------------------------------------------------------------------------
Softcore part of the system: 3 atoms, TEMP(K) = 0.00
SC_Etot= 0.2285 SC_EKtot= 0.0000 SC_EPtot = 0.2285
SC_BOND= 0.0293 SC_ANGLE= 0.0568 SC_DIHED = 0.1424
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 34.3341 SC_VDW_DER= -9.8131 SC_DERIV = 24.5210
------------------------------------------------------------------------------
| TI region 2
NSTEP = 0 TIME(PS) = 0.000 TEMP(K) = 0.00 PRESS = 0.0
Etot = -106290.2119 EKtot = 0.0000 EPtot = -106290.2119
BOND = 10916.9779 ANGLE = 122.0025 DIHED = 403.4883
1-4 NB = 153.0514 1-4 EEL = -3075.5267 VDWAALS = 20127.5335
EELEC = -134937.7969 EHBOND = 0.0000 RESTRAINT = 0.0582
EAMBER (non-restraint) = -106290.2700
DV/DL = 139.0082
------------------------------------------------------------------------------
Softcore part of the system: 4 atoms, TEMP(K) = 0.00
SC_Etot= 3.5272 SC_EKtot= 0.0000 SC_EPtot = 3.5272
SC_BOND= 0.0000 SC_ANGLE= 0.0828 SC_DIHED = 3.4444
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 34.3341 SC_VDW_DER= -9.8131 SC_DERIV = 24.5210
------------------------------------------------------------------------------
NMR restraints: Bond = 0.058 Angle = 0.000 Torsion = 0.000
===============================================================================
wrapping first mol.: -67.33224 0.00000 0.00000
wrapping first mol.: -67.33224 0.00000 0.00000
| TI region 1
NSTEP = 10000 TIME(PS) = 10.000 TEMP(K) = NaN PRESS = 0.0
Etot = NaN EKtot = NaN EPtot = **************
BOND = ************** ANGLE = 337.0443 DIHED = 450.5172
1-4 NB = 184.8223 1-4 EEL = -3070.5701 VDWAALS = 10559.7642
EELEC = -88347.5756 EHBOND = 0.0000 RESTRAINT = 75.2042
EAMBER (non-restraint) = **************
DV/DL = 143.1531
------------------------------------------------------------------------------
Softcore part of the system: 3 atoms, TEMP(K) = 297.22
SC_Etot= 4.3453 SC_EKtot= 2.6578 SC_EPtot = 1.6874
SC_BOND= 0.6219 SC_ANGLE= 0.1044 SC_DIHED = 0.9611
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 32.8690 SC_VDW_DER= -9.0955 SC_DERIV = 23.7735
------------------------------------------------------------------------------
| TI region 2
NSTEP = 10000 TIME(PS) = 10.000 TEMP(K) = NaN PRESS = 0.0
Etot = NaN EKtot = NaN EPtot = **************
BOND = ************** ANGLE = 337.0443 DIHED = 450.5172
1-4 NB = 184.8223 1-4 EEL = -3070.5701 VDWAALS = 10559.7642
EELEC = -88347.5756 EHBOND = 0.0000 RESTRAINT = 75.2042
EAMBER (non-restraint) = **************
DV/DL = 143.1531
------------------------------------------------------------------------------
Softcore part of the system: 4 atoms, TEMP(K) = 444.08
SC_Etot= 12.2731 SC_EKtot= 5.2948 SC_EPtot = 6.9783
SC_BOND= 0.2692 SC_ANGLE= 2.5118 SC_DIHED = 4.1973
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 32.8690 SC_VDW_DER= -9.0955 SC_DERIV = 23.7735
------------------------------------------------------------------------------
NMR restraints: Bond = 0.166 Angle = 0.000 Torsion = 0.000
===============================================================================
wrapping first mol.: -67.33224 0.00000 0.00000
wrapping first mol.: -67.33224 0.00000 0.00000
Amber24 p03
RTX A5000
heat.out:
--------------------------------------------------------------------------------
4. RESULTS
--------------------------------------------------------------------------------
DOF for the SC part 1 of the system: 9
DOF for the SC part 2 of the system: 12
| TI region 1
NSTEP = 0 TIME(PS) = 0.000 TEMP(K) = 146.63 PRESS = 0.0
Etot = -99444.2985 EKtot = 6860.7558 EPtot = -106305.0542
BOND = 10919.6424 ANGLE = 122.0038 DIHED = 403.4872
1-4 NB = 153.0703 1-4 EEL = -3075.5440 VDWAALS = 20137.9274
EELEC = -134965.6997 EHBOND = 0.0000 RESTRAINT = 0.0583
EAMBER (non-restraint) = -106305.1126
DV/DL = 139.0251
------------------------------------------------------------------------------
Softcore part of the system: 3 atoms, TEMP(K) = 745.66
SC_Etot= 6.8971 SC_EKtot= 6.6680 SC_EPtot = 0.2291
SC_BOND= 0.0292 SC_ANGLE= 0.0566 SC_DIHED = 0.1433
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 34.3772 SC_VDW_DER= -9.8395 SC_DERIV = 24.5376
------------------------------------------------------------------------------
| TI region 2
NSTEP = 0 TIME(PS) = 0.000 TEMP(K) = 146.62 PRESS = 0.0
Etot = -99444.2226 EKtot = 6860.8316 EPtot = -106305.0542
BOND = 10919.6424 ANGLE = 122.0038 DIHED = 403.4872
1-4 NB = 153.0703 1-4 EEL = -3075.5440 VDWAALS = 20137.9274
EELEC = -134965.6997 EHBOND = 0.0000 RESTRAINT = 0.0583
EAMBER (non-restraint) = -106305.1126
DV/DL = 139.0251
------------------------------------------------------------------------------
Softcore part of the system: 4 atoms, TEMP(K) = 565.61
SC_Etot= 10.2711 SC_EKtot= 6.7439 SC_EPtot = 3.5272
SC_BOND= 0.0000 SC_ANGLE= 0.0828 SC_DIHED = 3.4444
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 34.3772 SC_VDW_DER= -9.8395 SC_DERIV = 24.5376
------------------------------------------------------------------------------
NMR restraints: Bond = 0.058 Angle = 0.000 Torsion = 0.000
===============================================================================
wrapping first mol.: -67.33224 0.00000 0.00000
wrapping first mol.: -67.33224 0.00000 0.00000
| TI region 1
NSTEP = 10000 TIME(PS) = 10.000 TEMP(K) = NaN PRESS = 0.0
Etot = NaN EKtot = NaN EPtot = -79719.3320
BOND = 168.2637 ANGLE = 351.4225 DIHED = 453.4309
1-4 NB = 162.2674 1-4 EEL = -3094.2484 VDWAALS = 10565.1140
EELEC = -88399.8023 EHBOND = 0.0000 RESTRAINT = 74.2200
EAMBER (non-restraint) = -79793.5520
DV/DL = 127.5057
------------------------------------------------------------------------------
Softcore part of the system: 3 atoms, TEMP(K) = 226.18
SC_Etot= 6.2777 SC_EKtot= 2.0226 SC_EPtot = 4.2552
SC_BOND= 2.1754 SC_ANGLE= 0.5859 SC_DIHED = 1.4939
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 18.7750 SC_VDW_DER= -4.3177 SC_DERIV = 14.4573
------------------------------------------------------------------------------
| TI region 2
NSTEP = 10000 TIME(PS) = 10.000 TEMP(K) = NaN PRESS = 0.0
Etot = NaN EKtot = NaN EPtot = -79719.3320
BOND = 168.2637 ANGLE = 351.4225 DIHED = 453.4309
1-4 NB = 162.2674 1-4 EEL = -3094.2484 VDWAALS = 10565.1140
EELEC = -88399.8023 EHBOND = 0.0000 RESTRAINT = 74.2200
EAMBER (non-restraint) = -79793.5520
DV/DL = 127.5057
------------------------------------------------------------------------------
Softcore part of the system: 4 atoms, TEMP(K) = 305.75
SC_Etot= 10.6711 SC_EKtot= 3.6455 SC_EPtot = 7.0256
SC_BOND= 1.3274 SC_ANGLE= 1.5621 SC_DIHED = 4.1361
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 18.7750 SC_VDW_DER= -4.3177 SC_DERIV = 14.4573
------------------------------------------------------------------------------
NMR restraints: Bond = 0.066 Angle = 0.000 Torsion = 0.000
===============================================================================
wrapping first mol.: -67.33224 0.00000 0.00000
wrapping first mol.: -67.33224 0.00000 0.00000
| TI region 1
NSTEP = 20000 TIME(PS) = 20.000 TEMP(K) = NaN PRESS = 0.0
Etot = NaN EKtot = NaN EPtot = -79680.6221
BOND = 152.6742 ANGLE = 349.4495 DIHED = 474.1784
1-4 NB = 166.6676 1-4 EEL = -3077.0381 VDWAALS = 10416.5827
EELEC = -88246.5247 EHBOND = 0.0000 RESTRAINT = 83.3883
EAMBER (non-restraint) = -79764.0104
DV/DL = 135.9584
------------------------------------------------------------------------------
Softcore part of the system: 3 atoms, TEMP(K) = 293.71
SC_Etot= 5.6600 SC_EKtot= 2.6265 SC_EPtot = 3.0335
SC_BOND= 0.3299 SC_ANGLE= 0.9190 SC_DIHED = 1.7847
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 27.5456 SC_VDW_DER= -7.8929 SC_DERIV = 19.6527
------------------------------------------------------------------------------
| TI region 2
NSTEP = 20000 TIME(PS) = 20.000 TEMP(K) = NaN PRESS = 0.0
Etot = NaN EKtot = NaN EPtot = -79680.6221
BOND = 152.6742 ANGLE = 349.4495 DIHED = 474.1784
1-4 NB = 166.6676 1-4 EEL = -3077.0381 VDWAALS = 10416.5827
EELEC = -88246.5247 EHBOND = 0.0000 RESTRAINT = 83.3883
EAMBER (non-restraint) = -79764.0104
DV/DL = 135.9584
------------------------------------------------------------------------------
Softcore part of the system: 4 atoms, TEMP(K) = 109.81
SC_Etot= 8.0337 SC_EKtot= 1.3093 SC_EPtot = 6.7245
SC_BOND= 1.3112 SC_ANGLE= 1.0552 SC_DIHED = 4.3580
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 27.5456 SC_VDW_DER= -7.8929 SC_DERIV = 19.6527
------------------------------------------------------------------------------
NMR restraints: Bond = 0.152 Angle = 0.000 Torsion = 0.000
===============================================================================
wrapping first mol.: -67.33224 0.00000 0.00000
wrapping first mol.: -67.33224 0.00000 0.00000
Amber 20 p12
Tesla A40
heat.out:
--------------------------------------------------------------------------------
4. RESULTS
--------------------------------------------------------------------------------
DOF for the SC part 1 of the system: 9
DOF for the SC part 2 of the system: 12
| TI region 1
NSTEP = 0 TIME(PS) = 0.000 TEMP(K) = 147.58 PRESS = 0.0
Etot = -98965.1422 EKtot = 6905.2061 EPtot = -105870.3484
BOND = 10842.7479 ANGLE = 121.8447 DIHED = 403.6283
1-4 NB = 152.5132 1-4 EEL = -3075.0657 VDWAALS = 19846.6138
EELEC = -134162.6839 EHBOND = 0.0000 RESTRAINT = 0.0535
EAMBER (non-restraint) = -105870.4018
DV/DL = 138.4495
------------------------------------------------------------------------------
Softcore part of the system: 3 atoms, TEMP(K) = 817.57
SC_Etot= 7.5232 SC_EKtot= 7.3110 SC_EPtot = 0.2121
SC_BOND= 0.0309 SC_ANGLE= 0.0577 SC_DIHED = 0.1236
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 33.0600 SC_VDW_DER= -8.9555 SC_DERIV = 24.1045
------------------------------------------------------------------------------
| TI region 2
NSTEP = 0 TIME(PS) = 0.000 TEMP(K) = 147.58 PRESS = 0.0
Etot = -98964.5493 EKtot = 6905.7990 EPtot = -105870.3484
BOND = 10842.7479 ANGLE = 121.8447 DIHED = 403.6283
1-4 NB = 152.5132 1-4 EEL = -3075.0657 VDWAALS = 19846.6138
EELEC = -134162.6839 EHBOND = 0.0000 RESTRAINT = 0.0535
EAMBER (non-restraint) = -105870.4018
DV/DL = 138.4495
------------------------------------------------------------------------------
Softcore part of the system: 4 atoms, TEMP(K) = 662.87
SC_Etot= 11.4310 SC_EKtot= 7.9035 SC_EPtot = 3.5275
SC_BOND= 0.0000 SC_ANGLE= 0.0840 SC_DIHED = 3.4434
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 33.0600 SC_VDW_DER= -8.9555 SC_DERIV = 24.1045
------------------------------------------------------------------------------
NMR restraints: Bond = 0.053 Angle = 0.000 Torsion = 0.000
===============================================================================
wrapping first mol.: -67.33224 0.00000 0.00000
wrapping first mol.: -67.33224 0.00000 0.00000
| TI region 1
NSTEP = 10000 TIME(PS) = 10.000 TEMP(K) = 297.57 PRESS = 0.0
Etot = -65737.8910 EKtot = 13923.0436 EPtot = -79660.9346
BOND = 171.0275 ANGLE = 337.7617 DIHED = 470.6290
1-4 NB = 159.2908 1-4 EEL = -3085.0244 VDWAALS = 10404.9654
EELEC = -88190.9585 EHBOND = 0.0000 RESTRAINT = 71.3739
EAMBER (non-restraint) = -79732.3085
DV/DL = 133.7000
------------------------------------------------------------------------------
Softcore part of the system: 3 atoms, TEMP(K) = 383.83
SC_Etot= 7.0592 SC_EKtot= 3.4323 SC_EPtot = 3.6269
SC_BOND= 0.6855 SC_ANGLE= 0.7747 SC_DIHED = 2.1667
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 34.9878 SC_VDW_DER= -13.2377 SC_DERIV = 21.7501
------------------------------------------------------------------------------
| TI region 2
NSTEP = 10000 TIME(PS) = 10.000 TEMP(K) = 297.54 PRESS = 0.0
Etot = -65738.2559 EKtot = 13922.6787 EPtot = -79660.9346
BOND = 171.0275 ANGLE = 337.7617 DIHED = 470.6290
1-4 NB = 159.2908 1-4 EEL = -3085.0244 VDWAALS = 10404.9654
EELEC = -88190.9585 EHBOND = 0.0000 RESTRAINT = 71.3739
EAMBER (non-restraint) = -79732.3085
DV/DL = 133.7000
------------------------------------------------------------------------------
Softcore part of the system: 4 atoms, TEMP(K) = 257.26
SC_Etot= 8.4508 SC_EKtot= 3.0674 SC_EPtot = 5.3834
SC_BOND= 0.5147 SC_ANGLE= 1.2300 SC_DIHED = 3.6387
SC_14NB= 0.0000 SC_14EEL= 0.0000 SC_VDW = 0.0000
SC_EEL = 0.0000
SC_RES_DIST= 0.0000 SC_RES_ANG= 0.0000 SC_RES_TORS= 0.0000
SC_EEL_DER= 34.9878 SC_VDW_DER= -13.2377 SC_DERIV = 21.7501
------------------------------------------------------------------------------
NMR restraints: Bond = 0.074 Angle = 0.000 Torsion = 0.000
===============================================================================
wrapping first mol.: -67.33224 0.00000 0.00000
wrapping first mol.: -67.33224 0.00000 0.00000
--
Dr. Frank Beierlein
Friedrich-Alexander-Universitaet Erlangen-Nuernberg (FAU)
Zentrum für Nationales Hochleistungsrechnen (NHR.FAU)
Computer-Chemie-Centrum (CCC)
Naegelsbachstr. 25, Room 2.109
91052 Erlangen, Deutschland/Germany
Tel. +49(0)-9131-85 20415
frank.beierlein.fau.de
https://chemistry.nat.fau.eu/beierlein
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Received on Thu Aug 14 2025 - 07:00:02 PDT
