[gmx-users] free energy perturbation

[emathe at gmu.edu]

Hello,
I am attempting to introduce a mutation (I->L) in a small protein (87 
residues) via free energy perturbation.  I get a strange resulting 
structure, mainly the leucine that I should obtain does not resemble a 
leucine (it looks like a hybrid between I and L).  The following shows 
my mdp options and the changes I made to the topology file.  Thanks for 
any help,
Ewy

.mdp file:

constraints         =  all-bonds
constraint_algorithm=  lincs
unconstrained_start =  yes
integrator          =  md
tinit               =  0.0
dt                  =  0.002    ; ps !
nsteps              =  20000     ; total 40 ps.
nstxout             =  250
nstvout             =  1000
nstfout             =  0
nstlog              =  100
nstenergy           =  100
nstlist             =  10
ns_type             =  grid
rlist               =  1.0
rcoulomb            =  1.0
rvdw                =  1.0
; Temperature coupling is on in two groups
Tcoupl              =  berendsen
tc-grps             =  Protein  SOL
tau_t               =  0.1      0.1
ref_t               =  300      300
; Energy monitoring
energygrps          =  Protein  SOL
; Pressure coupling is now on
Pcoupl              =  no
; Generate velocites is off at 300 K.
gen_vel             =  no
gen_temp            =  300.0
gen_seed            =  173529

free_energy         =  yes
init_lambda         =  0
delta_lambda        =  0.0000005


.top file:
...
 742      N     47    ILE      N    285      -0.28    14.0067   N     
-0.28   14.0067
   743      H     47    ILE      H    285       0.28      1.008   H     
 0.28   1.008
   744     C1     47    ILE     CA    286          0     12.011   C1    
    0   12.001
   745     HC     47    ILE     HA    286          0      1.008   HC    
    0   1.008
   746     C1     47    ILE     CB    287          0     12.011   C2    
    0   12.001
   747     HC     47    ILE     HB    287          0      1.008   HC    
    0   1.008
   748     C2     47    ILE    CG1    288          0     12.011   HC    
    0   1.008
   749     HC     47    ILE   HG11    288          0      1.008   C1    
    0   12.011
   750     HC     47    ILE   HG12    288          0      1.008   HC    
    0   1.008
   751     C3     47    ILE    CG2    289          0     12.011   C3    
    0   12.011
   752     HC     47    ILE   HG21    289          0      1.008   HC    
    0   1.008
   753     HC     47    ILE   HG22    289          0      1.008   HC    
    0   1.008
   754     HC     47    ILE   HG23    289          0      1.008   HC    
    0   1.008
   755     C3     47    ILE     CD    290          0     12.011   C3    
    0   12.011
   756     HC     47    ILE    HD1    290          0      1.008   HC    
    0   1.008
   757     HC     47    ILE    HD2    290          0      1.008   HC    
    0   1.008
   758     HC     47    ILE    HD3    290          0      1.008   HC    
    0   1.008
   759      C     47    ILE      C    291       0.38     12.011   C     
 0.38   12.011
   760      O     47    ILE      O    291      -0.38    15.9994   O     
-0.38   15.9994
...