[gmx-users] need help with free energy of solvation calculation

Moore, Jonathan (J) JMoore2 at dow.com
Fri Jan 6 20:15:15 CET 2006


I'm trying to reproduce the free energy of solvation difference between
cellononaose and 2,3,6-trimethylcellononaose as reported in as a way to get
my feet wet for using GROMACS to calculate free energies in these types of
systems:

H. Yu, M. Amann, T. Hansson, J. Köhler, G. Wich, and W. F. van Gunsteren.
"Effect of methylation on the stability and solvation free energy of amylose
and cellulose fragments: a molecular dynamics study." Carbohydr. Res., 339,
1697-1709 (2004).
	http://dx.doi.org/10.1016/j.carres.2004.05.003

The reported value in Table 3 of that paper is 393 kJ per mol.  I tried to
calculate the value with Gromacs 3.3rc3 using thermodynamic integration with
soft cores (since the hydrogens that change to methyls have no sigma or
epsilon) and 20 lambda values between 0 and 1 (50 ps of equilibration
followed by 150 ps of production at each lambda value).  I have reasonable
confidence that I have the force field implemented correctly because I
calculated exactly the same values for the various energy terms as one of
the paper's authors did for a configuration of an isolated cellobiose
molecule provided by the author.  However, the free energy difference that I
calculated was the wrong sign and an order of magnitude too large, so I must
have done something very wrong.  One thing that has me perplexed is that if
I do a gmxdump of the .tpr file, it looks like the A and B states are
exactly the same for things like atom type, charge, and mass...suggesting
that I'm not specifying the B state successfully.  But if the A and B states
are exactly the same, then why am I getting anything at all for dgdl?  I'm
relatively new to GROMACS and have never done a coupling-parameter-type
calculation before.

I'll copy below the content of my .mdp file and the first part of my .itp
file.  Could someone with free energy experience have a look at them and let
me know if something looks wrong?  Also, how would you recommend that I try
to figure out what is going wrong?

.mdp
======
;
;	Input file
;
title               =  FE run
cpp                 =  /usr/bin/cpp
constraints         =  all-bonds
constraint_algorithm=  lincs
integrator          =  md
dt                  =  0.002	; ps !
nsteps              =  100000	; 
nstcomm             =  500
nstxout             =  10000
nstvout             =  10000
nstfout             =  0
nstlog              =  10000
nstenergy           =  250
nstxtcout           =  250
nstlist             =  5
ns_type             =  grid
rlist               =  0.8
coulombtype         =  Reaction-Field
rcoulomb            =  1.4
epsilon_r           =  78.5
vdwtype             =  Cut-off
rvdw                =  1.4
; temperature coupling is on in two groups
Tcoupl              =  nose-hoover
tc-grps		    =  polymer	SOL
tau_t               =  0.4	0.4
ref_t               =  300	300
; Energy monitoring
energygrps          =  polymer  SOL
; Isotropic pressure coupling is now on
Pcoupl              =  berendsen
Pcoupltype          = isotropic
tau_p               =  0.5
compressibility     =  4.5e-5
ref_p               =  1.01325
; Generate velocites is off at 300 K.
;gen_vel             =  no
;gen_temp            =  363.0
;gen_seed            =  173529
free_energy         =  yes
init_lambda               =  0.55
sc_alpha            =  1.51



.itp
===========
[ moleculetype ]
; name  nrexcl
cellononaose    3

[ atoms ]
;   nr    type   resnr  residu    atom    cgnr  charge
     1       H       1    H000     HO4       1   0.410
     2      OA       1    H000      O4       1  -0.642
     3     CH1       1    H000      C4       1   0.232
     4     CH1       1    H000      C3       2   0.232     CH1   0.180
     5      OA       1    H000      O3       2  -0.642      OA  -0.360
     6       H       1    H000     HO3       2   0.410     CH3   0.180
     7     CH1       1    H000      C2       3   0.232     CH1   0.180
     8      OA       1    H000      O2       3  -0.642      OA  -0.360
     9       H       1    H000     HO2       3   0.410     CH3   0.180
    10     CH2       1    H000      C6       4   0.232     CH2   0.180
    11      OA       1    H000      O6       4  -0.642      OA  -0.360
    12       H       1    H000     HO6       4   0.410     CH3   0.180
    13     CH1       1    H000      C5       5   0.376
    14      OA       1    H000      O5       5  -0.480
    15     CH1       1    H000      C1       5   0.232
    16      OA       1    H000      O1       5  -0.360
    17     CH1       2     000      C4       5   0.232
    18     CH1       2     000      C3       6   0.232     CH1   0.180
    19      OA       2     000      O3       6  -0.642      OA  -0.360
    20       H       2     000     HO3       6   0.410     CH3   0.180
    21     CH1       2     000      C2       7   0.232     CH1   0.180
    22      OA       2     000      O2       7  -0.642      OA  -0.360
    23       H       2     000     HO2       7   0.410     CH3   0.180
    24     CH2       2     000      C6       8   0.232     CH2   0.180
    25      OA       2     000      O6       8  -0.642      OA  -0.360
    26       H       2     000     HO6       8   0.410     CH3   0.180
    27     CH1       2     000      C5       9   0.376
    28      OA       2     000      O5       9  -0.480
    29     CH1       2     000      C1       9   0.232
    30      OA       2     000      O1       9  -0.360
    31     CH1       3     000      C4       9   0.232
    32     CH1       3     000      C3      10   0.232     CH1   0.180
    33      OA       3     000      O3      10  -0.642      OA  -0.360
    34       H       3     000     HO3      10   0.410     CH3   0.180
    35     CH1       3     000      C2      11   0.232     CH1   0.180
    36      OA       3     000      O2      11  -0.642      OA  -0.360
    37       H       3     000     HO2      11   0.410     CH3   0.180
    38     CH2       3     000      C6      12   0.232     CH2   0.180
    39      OA       3     000      O6      12  -0.642      OA  -0.360
    40       H       3     000     HO6      12   0.410     CH3   0.180
    41     CH1       3     000      C5      13   0.376
    42      OA       3     000      O5      13  -0.480
    43     CH1       3     000      C1      13   0.232
    44      OA       3     000      O1      13  -0.360
    45     CH1       4     000      C4      13   0.232
    46     CH1       4     000      C3      14   0.232     CH1   0.180
    47      OA       4     000      O3      14  -0.642      OA  -0.360
    48       H       4     000     HO3      14   0.410     CH3   0.180
    49     CH1       4     000      C2      15   0.232     CH1   0.180
    50      OA       4     000      O2      15  -0.642      OA  -0.360
    51       H       4     000     HO2      15   0.410     CH3   0.180
    52     CH2       4     000      C6      16   0.232     CH2   0.180
    53      OA       4     000      O6      16  -0.642      OA  -0.360
    54       H       4     000     HO6      16   0.410     CH3   0.180
    55     CH1       4     000      C5      17   0.376
    56      OA       4     000      O5      17  -0.480
    57     CH1       4     000      C1      17   0.232
    58      OA       4     000      O1      17  -0.360
    59     CH1       5     000      C4      17   0.232
    60     CH1       5     000      C3      18   0.232     CH1   0.180
    61      OA       5     000      O3      18  -0.642      OA  -0.360
    62       H       5     000     HO3      18   0.410     CH3   0.180
    63     CH1       5     000      C2      19   0.232     CH1   0.180
    64      OA       5     000      O2      19  -0.642      OA  -0.360
    65       H       5     000     HO2      19   0.410     CH3   0.180
    66     CH2       5     000      C6      20   0.232     CH2   0.180
    67      OA       5     000      O6      20  -0.642      OA  -0.360
    68       H       5     000     HO6      20   0.410     CH3   0.180
    69     CH1       5     000      C5      21   0.376
    70      OA       5     000      O5      21  -0.480
    71     CH1       5     000      C1      21   0.232
    72      OA       5     000      O1      21  -0.360
    73     CH1       6     000      C4      21   0.232
    74     CH1       6     000      C3      22   0.232     CH1   0.180
    75      OA       6     000      O3      22  -0.642      OA  -0.360
    76       H       6     000     HO3      22   0.410     CH3   0.180
    77     CH1       6     000      C2      23   0.232     CH1   0.180
    78      OA       6     000      O2      23  -0.642      OA  -0.360
    79       H       6     000     HO2      23   0.410     CH3   0.180
    80     CH2       6     000      C6      24   0.232     CH2   0.180
    81      OA       6     000      O6      24  -0.642      OA  -0.360
    82       H       6     000     HO6      24   0.410     CH3   0.180
    83     CH1       6     000      C5      25   0.376
    84      OA       6     000      O5      25  -0.480
    85     CH1       6     000      C1      25   0.232
    86      OA       6     000      O1      25  -0.360
    87     CH1       7     000      C4      25   0.232
    88     CH1       7     000      C3      26   0.232     CH1   0.180
    89      OA       7     000      O3      26  -0.642      OA  -0.360
    90       H       7     000     HO3      26   0.410     CH3   0.180
    91     CH1       7     000      C2      27   0.232     CH1   0.180
    92      OA       7     000      O2      27  -0.642      OA  -0.360
    93       H       7     000     HO2      27   0.410     CH3   0.180
    94     CH2       7     000      C6      28   0.232     CH2   0.180
    95      OA       7     000      O6      28  -0.642      OA  -0.360
    96       H       7     000     HO6      28   0.410     CH3   0.180
    97     CH1       7     000      C5      29   0.376
    98      OA       7     000      O5      29  -0.480
    99     CH1       7     000      C1      29   0.232
   100      OA       7     000      O1      29  -0.360
   101     CH1       8     000      C4      29   0.232
   102     CH1       8     000      C3      30   0.232     CH1   0.180
   103      OA       8     000      O3      30  -0.642      OA  -0.360
   104       H       8     000     HO3      30   0.410     CH3   0.180
   105     CH1       8     000      C2      31   0.232     CH1   0.180
   106      OA       8     000      O2      31  -0.642      OA  -0.360
   107       H       8     000     HO2      31   0.410     CH3   0.180
   108     CH2       8     000      C6      32   0.232     CH2   0.180
   109      OA       8     000      O6      32  -0.642      OA  -0.360
   110       H       8     000     HO6      32   0.410     CH3   0.180
   111     CH1       8     000      C5      33   0.376
   112      OA       8     000      O5      33  -0.480
   113     CH1       8     000      C1      33   0.232
   114      OA       8     000      O1      33  -0.360
   115     CH1       9    T000      C4      33   0.232
   116     CH1       9    T000      C3      34   0.232     CH1   0.180
   117      OA       9    T000      O3      34  -0.642      OA  -0.360
   118       H       9    T000     HO3      34   0.410     CH3   0.180
   119     CH1       9    T000      C2      35   0.232     CH1   0.180
   120      OA       9    T000      O2      35  -0.642      OA  -0.360
   121       H       9    T000     HO2      35   0.410     CH3   0.180
   122     CH2       9    T000      C6      36   0.232     CH2   0.180
   123      OA       9    T000      O6      36  -0.642      OA  -0.360
   124       H       9    T000     HO6      36   0.410     CH3   0.180
   125     CH1       9    T000      C5      37   0.376
   126      OA       9    T000      O5      37  -0.480
   127     CH1       9    T000      C1      37   0.232
   128      OA       9    T000      O1      37  -0.538
   129       H       9    T000     HO1      37   0.410

[ bonds ]
;  ai    aj funct  type
    1     2     2   gb_1
    5     6     2   gb_1  gb_19
    8     9     2   gb_1  gb_19
   11    12     2   gb_1  gb_19
    2     3     2  gb_19
    3     4     2  gb_25
    3    13     2  gb_25
    4     5     2  gb_19
    4     7     2  gb_25
    7     8     2  gb_19
    7    15     2  gb_25
   10    11     2  gb_19
   10    13     2  gb_25
   13    14     2  gb_19
   14    15     2  gb_19
   15    16     2  gb_19
   16    17     2  gb_19
   19    20     2   gb_1  gb_19
   22    23     2   gb_1  gb_19
   25    26     2   gb_1  gb_19
   17    18     2  gb_25
   17    27     2  gb_25
   18    19     2  gb_19
   18    21     2  gb_25
   21    22     2  gb_19
   21    29     2  gb_25
   24    25     2  gb_19
   24    27     2  gb_25
   27    28     2  gb_19
   28    29     2  gb_19
   29    30     2  gb_19
   30    31     2  gb_19
   33    34     2   gb_1  gb_19
   36    37     2   gb_1  gb_19
   39    40     2   gb_1  gb_19
   31    32     2  gb_25
   31    41     2  gb_25
   32    33     2  gb_19
   32    35     2  gb_25
   35    36     2  gb_19
   35    43     2  gb_25
   38    39     2  gb_19
   38    41     2  gb_25
   41    42     2  gb_19
   42    43     2  gb_19
   43    44     2  gb_19
   44    45     2  gb_19
   47    48     2   gb_1  gb_19
   50    51     2   gb_1  gb_19
   53    54     2   gb_1  gb_19
   45    46     2  gb_25
   45    55     2  gb_25
   46    47     2  gb_19
   46    49     2  gb_25
   49    50     2  gb_19
   49    57     2  gb_25
   52    53     2  gb_19
   52    55     2  gb_25
   55    56     2  gb_19
   56    57     2  gb_19
   57    58     2  gb_19
   58    59     2  gb_19
   61    62     2   gb_1  gb_19
   64    65     2   gb_1  gb_19
   67    68     2   gb_1  gb_19
   59    60     2  gb_25
   59    69     2  gb_25
   60    61     2  gb_19
   60    63     2  gb_25
   63    64     2  gb_19
   63    71     2  gb_25
   66    67     2  gb_19
   66    69     2  gb_25
   69    70     2  gb_19
   70    71     2  gb_19
   71    72     2  gb_19
   72    73     2  gb_19
   75    76     2   gb_1  gb_19
   78    79     2   gb_1  gb_19
   81    82     2   gb_1  gb_19
   73    74     2  gb_25
   73    83     2  gb_25
   74    75     2  gb_19
   74    77     2  gb_25
   77    78     2  gb_19
   77    85     2  gb_25
   80    81     2  gb_19
   80    83     2  gb_25
   83    84     2  gb_19
   84    85     2  gb_19
   85    86     2  gb_19
   86    87     2  gb_19
   89    90     2   gb_1  gb_19
   92    93     2   gb_1  gb_19
   95    96     2   gb_1  gb_19
   87    88     2  gb_25
   87    97     2  gb_25
   88    89     2  gb_19
   88    91     2  gb_25
   91    92     2  gb_19
   91    99     2  gb_25
   94    95     2  gb_19
   94    97     2  gb_25
   97    98     2  gb_19
   98    99     2  gb_19
   99   100     2  gb_19
  100   101     2  gb_19
  103   104     2   gb_1  gb_19
  106   107     2   gb_1  gb_19
  109   110     2   gb_1  gb_19
  101   102     2  gb_25
  101   111     2  gb_25
  102   103     2  gb_19
  102   105     2  gb_25
  105   106     2  gb_19
  105   113     2  gb_25
  108   109     2  gb_19
  108   111     2  gb_25
  111   112     2  gb_19
  112   113     2  gb_19
  113   114     2  gb_19
  114   115     2  gb_19
  117   118     2   gb_1  gb_19
  120   121     2   gb_1  gb_19
  123   124     2   gb_1  gb_19
  128   129     2   gb_1
  115   116     2  gb_25
  115   125     2  gb_25
  116   117     2  gb_19
  116   119     2  gb_25
  119   120     2  gb_19
  119   127     2  gb_25
  122   123     2  gb_19
  122   125     2  gb_25
  125   126     2  gb_19
  126   127     2  gb_19
  127   128     2  gb_19

Thanks,
Jonathan

____________________________
Jonathan Moore, Ph.D.
Research and Engineering Sciences - New Products
Core R&D
The Dow Chemical Company
1702 Building, Office 4E
Midland, MI 48674  USA
Phone:  (989) 636-9765 
Fax: (989) 636-4019
E Mail: jmoore2 at dow.com




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