[gmx-users] Protein in SDS, GROMOS96 ff, MD crash - SDS molecule comes apart, LINCS error

Venky Krishna venky.agas at gmail.com
Wed Apr 25 04:15:54 CEST 2007


Hi gmx-users,

System Setup:
My System consists of a one helix of a transmembrane protein + 58 SDS  
molecules + water + ions. (added in that order)
I energy minimized the system (using l-bfgs algorithm) after addition  
of each set of molecules to the box, starting from just the protein  
in the box. The potential energy was minimized well (to a negative  
value) and the Fmax on the atoms was < 50 as stated in the em.mdp file.
Next I equilibrated the system for 1 ns by doing a position  
restrained MD (protein restrained), to relax the SDS molecules around  
the protein (NVT equilibration) using berendsen thermostat.
Later NPT md simulation was started by linearly heating the system  
thus obtained from NVT equilibration from 0 K to 300 K in 50 ps. the  
rest of the 10 ns the temperature was kept at 300 K using nose-hoover  
thermostat. Pressure coupling using parrinello-rahman.

Problem:
So here is the problem... after 500 ps, a SDS molecule rips apart and  
the simulation crashes with LINCS error. Quite surprisingly, there  
was only one SDS molecule showing such instability... all other  
molecules are intact. any inputs on how to correct the problem... for  
now I just deleted the SDS molecule, equilibrated the system for 200  
ps and rerun the MD simulation... I have a bad feeling it will crash  
again.

Parameters:
I generated the SDS topology using PRODRG2 BETA server.. since I  
wanted GROMOS96 parameters. Here is how the SDS top file looks like.

~~~~~~~~~~~~~~~~~~~~
[ moleculetype ]
; Name nrexcl
SDS      3

[ atoms ]
;   nr      type  resnr resid  atom  cgnr   charge     mass
      1        OA     1  SDS     OAD     1   -0.726  15.9994
      2     SDMSO     1  SDS     SAQ     1    2.226  32.0600
      3        OM     1  SDS     OAB     1   -1.179  15.9994
      4        OM     1  SDS     OAC     1   -1.179  15.9994
      5        OA     1  SDS     OAP     1   -0.207  15.9994
      6       CH2     1  SDS     CAO     1    0.033  14.0270
      7       CH2     1  SDS     CAN     1    0.032  14.0270
      8       CH2     1  SDS     CAM     2    0.000  14.0270
      9       CH2     1  SDS     CAL     2    0.000  14.0270
     10       CH2     1  SDS     CAK     2    0.000  14.0270
     11       CH2     1  SDS     CAJ     2    0.000  14.0270
     12       CH2     1  SDS     CAI     3    0.007  14.0270
     13       CH2     1  SDS     CAH     3    0.006  14.0270
     14       CH2     1  SDS     CAG     3    0.008  14.0270
     15       CH2     1  SDS     CAF     3    0.007  14.0270
     16       CH2     1  SDS     CAE     3    0.007  14.0270
     17       CH3     1  SDS     CAA     3   -0.035  15.0350

[ bonds ]
; ai  aj  fu    c0, c1, ...
    1   2   2    0.144   6100000.0    0.144   6100000.0 ;   OAD  SAQ
    2   3   2    0.153   8040000.0    0.153   8040000.0 ;   SAQ  OAB
    2   4   2    0.153   8040000.0    0.153   8040000.0 ;   SAQ  OAC
    2   5   2    0.144   6100000.0    0.144   6100000.0 ;   SAQ  OAP
    5   6   2    0.143   8180000.0    0.143   8180000.0 ;   OAP  CAO
    6   7   2    0.153   7150000.0    0.153   7150000.0 ;   CAO  CAN
    7   8   2    0.153   7150000.0    0.153   7150000.0 ;   CAN  CAM
    8   9   2    0.153   7150000.0    0.153   7150000.0 ;   CAM  CAL
    9  10   2    0.153   7150000.0    0.153   7150000.0 ;   CAL  CAK
   10  11   2    0.153   7150000.0    0.153   7150000.0 ;   CAK  CAJ
   11  12   2    0.153   7150000.0    0.153   7150000.0 ;   CAJ  CAI
   12  13   2    0.153   7150000.0    0.153   7150000.0 ;   CAI  CAH
   13  14   2    0.153   7150000.0    0.153   7150000.0 ;   CAH  CAG
   14  15   2    0.153   7150000.0    0.153   7150000.0 ;   CAG  CAF
   15  16   2    0.153   7150000.0    0.153   7150000.0 ;   CAF  CAE
   16  17   2    0.153   7150000.0    0.153   7150000.0 ;   CAE  CAA

[ pairs ]
; ai  aj  fu    c0, c1, ...
    1   6   1                                           ;   OAD  CAO
    2   7   1                                           ;   SAQ  CAN
    3   6   1                                           ;   OAB  CAO
    4   6   1                                           ;   OAC  CAO
    5   8   1                                           ;   OAP  CAM
    6   9   1                                           ;   CAO  CAL
    7  10   1                                           ;   CAN  CAK
    8  11   1                                           ;   CAM  CAJ
    9  12   1                                           ;   CAL  CAI
   10  13   1                                           ;   CAK  CAH
   11  14   1                                           ;   CAJ  CAG
   12  15   1                                           ;   CAI  CAF
   13  16   1                                           ;   CAH  CAE
   14  17   1                                           ;   CAG  CAA

[ angles ]
; ai  aj  ak  fu    c0, c1, ...
    1   2   3   2    109.5       518.0    109.5       518.0 ;   OAD   
SAQ  OAB
    1   2   4   2    109.5       518.0    109.5       518.0 ;   OAD   
SAQ  OAC
    1   2   5   2    109.5       518.0    109.5       518.0 ;   OAD   
SAQ  OAP
    3   2   4   2    109.5       518.0    109.5       518.0 ;   OAB   
SAQ  OAC
    3   2   5   2    109.5       518.0    109.5       518.0 ;   OAB   
SAQ  OAP
    4   2   5   2    109.5       518.0    109.5       518.0 ;   OAC   
SAQ  OAP
    2   5   6   2    120.0       530.0    120.0       530.0 ;   SAQ   
OAP  CAO
    5   6   7   2    109.5       520.0    109.5       520.0 ;   OAP   
CAO  CAN
    6   7   8   2    109.5       520.0    109.5       520.0 ;   CAO   
CAN  CAM
    7   8   9   2    109.5       520.0    109.5       520.0 ;   CAN   
CAM  CAL
    8   9  10   2    109.5       520.0    109.5       520.0 ;   CAM   
CAL  CAK
    9  10  11   2    109.5       520.0    109.5       520.0 ;   CAL   
CAK  CAJ
   10  11  12   2    109.5       520.0    109.5       520.0 ;   CAK   
CAJ  CAI
   11  12  13   2    109.5       520.0    109.5       520.0 ;   CAJ   
CAI  CAH
   12  13  14   2    109.5       520.0    109.5       520.0 ;   CAI   
CAH  CAG
   13  14  15   2    109.5       520.0    109.5       520.0 ;   CAH   
CAG  CAF
   14  15  16   2    109.5       520.0    109.5       520.0 ;   CAG   
CAF  CAE
   15  16  17   2    109.5       520.0    109.5       520.0 ;   CAF   
CAE  CAA

[ dihedrals ]
; ai  aj  ak  al  fu    c0, c1, m, ...
    2   1   3   4   2     35.3  334.8       35.3  334.8   ; imp    
SAQ  OAD  OAB  OAC
    1   2   5   6   1      0.0    1.3 3      0.0    1.3 3 ; dih    
OAD  SAQ  OAP  CAO
    7   6   5   2   1      0.0    1.3 3      0.0    1.3 3 ; dih    
CAN  CAO  OAP  SAQ
    8   7   6   5   1      0.0    5.9 3      0.0    5.9 3 ; dih    
CAM  CAN  CAO  OAP
    9   8   7   6   1      0.0    5.9 3      0.0    5.9 3 ; dih    
CAL  CAM  CAN  CAO
   10   9   8   7   1      0.0    5.9 3      0.0    5.9 3 ; dih    
CAK  CAL  CAM  CAN
   11  10   9   8   1      0.0    5.9 3      0.0    5.9 3 ; dih    
CAJ  CAK  CAL  CAM
   12  11  10   9   1      0.0    5.9 3      0.0    5.9 3 ; dih    
CAI  CAJ  CAK  CAL
   13  12  11  10   1      0.0    5.9 3      0.0    5.9 3 ; dih    
CAH  CAI  CAJ  CAK
   14  13  12  11   1      0.0    5.9 3      0.0    5.9 3 ; dih    
CAG  CAH  CAI  CAJ
   15  14  13  12   1      0.0    5.9 3      0.0    5.9 3 ; dih    
CAF  CAG  CAH  CAI
   16  15  14  13   1      0.0    5.9 3      0.0    5.9 3 ; dih    
CAE  CAF  CAG  CAH
   17  16  15  14   1      0.0    5.9 3      0.0    5.9 3 ; dih    
CAA  CAE  CAF  CAG
~~~~~~~~~~~~~~~~~~~~
and here are my relevant MD mdp parameters.

####################

integrator               	= md
tinit                    	= 0
dt                       	= 0.002
nsteps                   	= 5000000
init_step              	= 0
nstlist           	       	= 5
ns-type     	             	= grid
pbc                      	= xyz
rlist                    	= 0.9
domain-decomposition     = no
coulombtype             = pme
rcoulomb                 	= 0.9
epsilon-r               	= 1
vdw-type                 	= Cut-off
rvdw-switch              = 0
rvdw                     	= 1.4
DispCorr                 = No

table-extension          = 1
fourierspacing           = 0.12
fourier_nx               = 0
fourier_ny               = 0
fourier_nz               = 0

; EWALD/PME/PPPM parameters
pme_order                = 4
ewald_rtol               	= 1e-05
ewald_geometry        = 3d
epsilon_surface         = 0
optimize_fft             	= yes

; OPTIONS FOR WEAK COUPLING ALGORITHMS
tcoupl                   	= nose-hoover
tc-grps                  	= Protein      SDS     SOL     Na+     Cl-
tau-t                    	= 0.5          0.5     0.5     0.5     0.5
ref-t                    	= 300          300     300     300     300

Pcoupl                   	= Parrinello-Rahman
Pcoupltype               = Isotropic
tau-p                    	= 5
compressibility          = 4.5e-5
ref-p                    	= 1
andersen_seed           = 815131

; SIMULATED ANNEALING
; Type of annealing for each temperature group (no/single/periodic)
annealing                = single single single single single
; Number of time points to use for specifying annealing in each group
annealing_npoints        = 2 2 2 2 2
; List of times at the annealing points for each group
annealing_time           = 0 20 0 20 0 20 0 20 0 20
; Temp. at each annealing point, for each group.
annealing_temp           = 0 300 0 300 0 300 0 300 0 300

; GENERATE VELOCITIES FOR STARTUP RUN
gen-vel                  	= yes
gen-temp                 	= 0
gen-seed                 	= 3529

; OPTIONS FOR BONDS
constraints              		= all-bonds
constraint-algorithm     	= Lincs
unconstrained-start    	= no
lincs-order             		= 4
lincs-iter               		= 1
lincs-warnangle          	= 30
morse                    		= no

####################

Here is the ERROR....
$$$$$$$$$$$$$$$$$$$$$$$$$$$

Step 257327, time 514.654 (ps)  LINCS WARNING
relative constraint deviation after LINCS:
max 25.765928 (between atoms 920 and 921) rms 1.109525
bonds that rotated more than 30 degrees:
atom 1 atom 2  angle  previous, current, constraint length
     920    921   92.7    0.1507   3.8543      0.1440
     921    922  119.1    0.1556   0.3664      0.1530
     921    923   78.8    0.1442   0.1825      0.1530
     921    924  100.1    0.1613   1.1378      0.1440
     924    925   92.9    0.1390   3.1287      0.1430
     925    926   92.6    0.1870   3.1463      0.1530
     926    927  157.8    0.1521   0.1948      0.1530
     927    928  128.2    0.1545   0.2347      0.1530
     928    929   63.1    0.1529   0.1001      0.1530
Constraint error in algorithm Lincs at step 257327

Step 257328, time 514.656 (ps)  LINCS WARNING
relative constraint deviation after LINCS:
max 390842875904.000000 (between atoms 924 and 925) rms  
20729815040.000000
bonds that rotated more than 30 degrees:
atom 1 atom 2  angle  previous, current, constraint length
     699    700  118.2    0.1440   0.3004      0.1440
     700    701   99.2    0.1530   0.9467      0.1530
     700    702   62.8    0.1530   0.1665      0.1530
     700    703   77.7    0.1440   0.1298      0.1440
     703    704   31.6    0.1430   0.1368      0.1430
     716    717   90.5    0.1440  34.8807      0.1440
     717    718   90.1    0.1530 147.2678      0.1530
     717    719   90.1    0.1530 110.9749      0.1530
     717    720   90.9    0.1440  36.1724      0.1440
     720    721   91.5    0.1430  10.8505      0.1430
     721    722   97.2    0.1530   2.9375      0.1530
     722    723  145.7    0.1530   0.2025      0.1530
     723    724   42.0    0.1530   0.1993      0.1530
     886    887   57.6    0.1440   0.1784      0.1440
     887    888   67.3    0.1530   0.2050      0.1530
     887    889   63.1    0.1530   0.1974      0.1530
     887    890  100.5    0.1440   0.8066      0.1440
     890    891  100.0    0.1430   0.7412      0.1430
     891    892  155.6    0.1530   0.1709      0.1530
     892    893   42.1    0.1530   0.2004      0.1530
     903    904   90.9    0.1440 15469.8779      0.1440
     904    905   90.1    0.1530 51128.5117      0.1530
     904    906   90.2    0.1530 46422.8555      0.1530
     904    907   90.1    0.1440 134111.4688      0.1440
     907    908   90.1    0.1430 168917.5156      0.1430
     908    909   90.3    0.1530 16148.1357      0.1530
     909    910   93.8    0.1530 687.8440      0.1530
     910    911   93.1    0.1530 101.2424      0.1530
     911    912  108.5    0.1530  14.7890      0.1530
     913    914  130.7    0.1530   0.6334      0.1530
     914    915   59.3    0.1530   0.2331      0.1530
     920    921  124.5    3.8543 590567680.0000      0.1440
     921    922  115.9    0.3664 507195392.0000      0.1530
     921    923  127.3    0.1825 597398592.0000      0.1530
     921    924   89.6    1.1378 54504730624.0000      0.1440
     924    925   94.0    3.1287 55890534400.0000      0.1430
     925    926   94.6    3.1463 52505100288.0000      0.1530
     926    927   91.7    0.1948 53183660032.0000      0.1530
     927    928   50.6    0.2347 1845543040.0000      0.1530
     928    929   58.1    0.1001 2104577408.0000      0.1530
     929    930  162.9    0.1506 350578240.0000      0.1530
     930    931   31.0    0.1543 339091040.0000      0.1530
     931    932   86.4    0.1530   0.3569      0.1530
     932    933   44.6    0.1531   0.2167      0.1530
    1117   1118   65.7    0.1530   0.2308      0.1530
    1118   1119  106.3    0.1530   0.5409      0.1530
    1119   1120  104.2    0.1530   0.6235      0.1530
    1120   1121   98.6    0.1530   1.0182      0.1530
    1121   1122   95.9    0.1530   1.4904      0.1530
    1122   1123   95.0    0.1530   1.7516      0.1530
    1124   1125  107.3    0.1440   0.4820      0.1440
    1125   1126  107.7    0.1530   0.5021      0.1530
    1125   1127  107.1    0.1530   0.5176      0.1530
    1125   1128  104.5    0.1440   0.5717      0.1440
    1128   1129   78.4    0.1430   0.2178      0.1430
    1129   1130   63.6    0.1530   0.1758      0.1530
    1130   1131   53.0    0.1530   0.1784      0.1530
    1131   1132   40.3    0.1530   0.1644      0.1530
Constraint error in algorithm Lincs at step 257328

t = 514.656 ps: Water molecule starting at atom 18916 can not be  
settled.
Check for bad contacts and/or reduce the timestep.Wrote pdb files  
with previous and current coordinates
Large VCM(group rest): 24544858112.00000, -56862011392.00000,  
610747392.00000, ekin-cm:  2.45315e+26
Group rest with mass  1.27898e+05, Ekrot  1.46688e+15 Det(I)  
=          nan
   COM: 49089732.00000  -113724048.00000  1221496.62500
   P:   3139232935706624.00000  -7272524777783296.00000   
78113232912384.00000
   V:   24544858112.00000  -56862011392.00000  610747392.00000
   J:   -162155133050814464.00000  83557368560651075584.00000   
-184521431156065828864.00000
   w:       -0.00001       0.00002      -0.00001
Inertia tensor (3x3):
    Inertia tensor[    0]={ 1.59138e+25, -2.53183e+25,  6.93924e+24}
    Inertia tensor[    1]={-2.53183e+25,  4.38301e+25, -1.26821e+25}
    Inertia tensor[    2]={ 6.93924e+24, -1.26821e+25,  8.36827e+24}

$$$$$$$$$$$$$$$$$$$$$$$$$$

Regards,

Venky.

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