[gmx-users] Question about gmx bar

Thanh Le thanh.q.le at sjsu.edu
Tue Feb 27 22:13:29 CET 2018


Hi everyone, 
I just finished running 2 sets of simulations (ligand in water and RNA+ligand in water) for my system to learn about its binding energy. Using the parameter for BAR method, I ran 20 simulations for ligand in water and 30 simulations for RNA+ligand in water with different lambda stages. What is interesting/confusing to me is the 0 energy from stages 0-10. Based on what I have been reading and the set up of my prod.mdp, these stages should give Coulomb Energy. If you can tell me why or how to fix it, I would greatly appreciate your help.
point      0 -      1,   DG  0.00 +/-  0.00
point      1 -      2,   DG  0.00 +/-  0.00
point      2 -      3,   DG  0.00 +/-  0.00
point      3 -      4,   DG  0.00 +/-  0.00
point      4 -      5,   DG  0.00 +/-  0.00
point      5 -      6,   DG  0.00 +/-  0.00
point      6 -      7,   DG  0.00 +/-  0.00
point      7 -      8,   DG  0.00 +/-  0.00
point      8 -      9,   DG  0.00 +/-  0.00
point      9 -     10,   DG  0.00 +/-  0.00
point     10 -     11,   DG 1198.03 +/- 11.41
point     11 -     12,   DG 711.32 +/-  1.58
point     12 -     13,   DG 258.19 +/-  3.80
point     13 -     14,   DG -116.21 +/-  3.81
point     14 -     15,   DG 24.24 +/-  0.17
point     15 -     16,   DG 25.40 +/-  0.18
point     16 -     17,   DG 51.57 +/-  0.42
point     17 -     18,   DG 51.20 +/-  0.57
point     18 -     19,   DG 48.42 +/-  0.97
point     19 -     20,   DG 46.55 +/-  0.56
point     20 -     21,   DG 44.53 +/-  0.23
point     21 -     22,   DG 20.56 +/-  0.12
point     22 -     23,   DG 18.23 +/-  0.11
point     23 -     24,   DG 13.64 +/-  0.16
point     24 -     25,   DG -3.58 +/-  0.84
point     25 -     26,   DG -44.60 +/-  0.29
point     26 -     27,   DG -33.45 +/-  0.07
point     27 -     28,   DG -15.22 +/-  0.02
point     28 -     29,   DG  0.81 +/-  0.12

total      0 -     29,   DG 2299.63 +/-  5.17

Here is the prod.mdp for complex:

;====================================================
; Production simulation
;====================================================

;----------------------------------------------------
; RUN CONTROL
;----------------------------------------------------
integrator   = sd            ; stochastic leap-frog integrator
nsteps       = 50000000        ; 2 * 500,000 fs = 1000 ps = 1 ns
dt           = 0.002         ; 2 fs
comm-mode    = Linear        ; remove center of mass translation
nstcomm      = 100           ; frequency for center of mass motion removal

;----------------------------------------------------
; OUTPUT CONTROL
;----------------------------------------------------
nstxout                = 0          ; don't save coordinates to .trr
nstvout                = 0          ; don't save velocities to .trr
nstfout                = 0          ; don't save forces to .trr
nstxout-compressed     = 1000       ; xtc compressed trajectory output every 1000 steps (2 ps)
compressed-x-precision = 1000       ; precision with which to write to the compressed trajectory file
nstlog                 = 1000       ; update log file every 2 ps
nstenergy              = 1000       ; save energies every 2 ps
nstcalcenergy          = 100        ; calculate energies every 100 steps

;----------------------------------------------------
; BONDS
;----------------------------------------------------
constraint_algorithm   = lincs      ; holonomic constraints
constraints            = all-bonds  ; hydrogens only are constrained
lincs_iter             = 1          ; accuracy of LINCS (1 is default)
lincs_order            = 4          ; also related to accuracy (4 is default)
lincs-warnangle        = 30         ; maximum angle that a bond can rotate before LINCS will complain (30 is default)
continuation           = yes        ; formerly known as 'unconstrained-start' - useful for exact continuations and reruns

;----------------------------------------------------
; NEIGHBOR SEARCHING
;----------------------------------------------------
cutoff-scheme   = Verlet
ns-type         = grid   ; search neighboring grid cells
nstlist         = 10     ; 20 fs (default is 10)
rlist           = 1.0    ; short-range neighborlist cutoff (in nm)
pbc             = xyz    ; 3D PBC

;----------------------------------------------------
; ELECTROSTATICS
;----------------------------------------------------
coulombtype      = PME      ; Particle Mesh Ewald for long-range electrostatics
rcoulomb         = 1.0      ; short-range electrostatic cutoff (in nm)
ewald_geometry   = 3d       ; Ewald sum is performed in all three dimensions
pme-order        = 6        ; interpolation order for PME (default is 4)
fourierspacing   = 0.10     ; grid spacing for FFT
ewald-rtol       = 1e-6     ; relative strength of the Ewald-shifted direct potential at rcoulomb

;----------------------------------------------------
; VDW
;----------------------------------------------------
vdw-type                = PME
rvdw                    = 1.0
vdw-modifier            = Potential-Shift
ewald-rtol-lj           = 1e-3
lj-pme-comb-rule        = Geometric
DispCorr                = EnerPres

;----------------------------------------------------
; TEMPERATURE & PRESSURE COUPL
;----------------------------------------------------
tc_grps          = System
tau_t            = 1.0
ref_t            = 300
pcoupl           = Parrinello-Rahman
pcoupltype       = isotropic            ; uniform scaling of box vectors
tau_p            = 2                    ; time constant (ps)
ref_p            = 1.0                  ; reference pressure (bar)
compressibility  = 4.5e-05              ; isothermal compressibility of water (bar^-1)

;----------------------------------------------------
; VELOCITY GENERATION
;----------------------------------------------------
gen_vel      = no       ; Velocity generation is off

;----------------------------------------------------
; FREE ENERGY CALCULATIONS
;----------------------------------------------------
free-energy              = yes
couple-moltype           = Protein_chain_B
couple-lambda0           = vdw-q
couple-lambda1           = none
couple-intramol          = yes
separate-dhdl-file       = yes
sc-alpha                 = 0.5
sc-power                 = 1
sc-sigma		             = 0.3
init-lambda-state        = 0
bonded-lambdas           = 0.0 0.01 0.025 0.05 0.075 0.1 0.2 0.35 0.5 0.75 1.0 1.00 1.0 1.00 1.0 1.00 1.0 1.0 1.0 1.0 1.0 1.0 1.00 1.0 1.00 1.0 1.00 1.0 1.00 1.0
coul-lambdas             = 0.0 0.00 0.000 0.00 0.000 0.0 0.0 0.00 0.0 0.00 0.0 0.25 0.5 0.75 1.0 1.00 1.0 1.0 1.0 1.0 1.0 1.0 1.00 1.0 1.00 1.0 1.00 1.0 1.00 1.0
vdw-lambdas              = 0.0 0.00 0.000 0.00 0.000 0.0 0.0 0.00 0.0 0.00 0.0 0.00 0.0 0.00 0.0 0.05 0.1 0.2 0.3 0.4 0.5 0.6 0.65 0.7 0.75 0.8 0.85 0.9 0.95 1.0
nstdhdl                  = 100
calc-lambda-neighbors    = -1


Here is the prod.mdp for ligand

;====================================================
; Production simulation
;====================================================

;----------------------------------------------------
; RUN CONTROL
;----------------------------------------------------
integrator   = sd            ; stochastic leap-frog integrator
nsteps       = 50000000        ; 2 * 500,000 fs = 1000 ps = 1 ns
dt           = 0.002         ; 2 fs
comm-mode    = Linear        ; remove center of mass translation
nstcomm      = 100           ; frequency for center of mass motion removal

;----------------------------------------------------
; OUTPUT CONTROL
;----------------------------------------------------
nstxout                = 0          ; don't save coordinates to .trr
nstvout                = 0          ; don't save velocities to .trr
nstfout                = 0          ; don't save forces to .trr
nstxout-compressed     = 1000       ; xtc compressed trajectory output every 1000 steps (2 ps)
compressed-x-precision = 1000       ; precision with which to write to the compressed trajectory file
nstlog                 = 1000       ; update log file every 2 ps
nstenergy              = 1000       ; save energies every 2 ps
nstcalcenergy          = 100        ; calculate energies every 100 steps

;----------------------------------------------------
; BONDS
;----------------------------------------------------
constraint_algorithm   = lincs      ; holonomic constraints
constraints            = all-bonds  ; hydrogens only are constrained
lincs_iter             = 1          ; accuracy of LINCS (1 is default)
lincs_order            = 4          ; also related to accuracy (4 is default)
lincs-warnangle        = 30         ; maximum angle that a bond can rotate before LINCS will complain (30 is default)
continuation           = yes        ; formerly known as 'unconstrained-start' - useful for exact continuations and reruns

;----------------------------------------------------
; NEIGHBOR SEARCHING
;----------------------------------------------------
cutoff-scheme   = Verlet
ns-type         = grid   ; search neighboring grid cells
nstlist         = 10     ; 20 fs (default is 10)
rlist           = 1.0    ; short-range neighborlist cutoff (in nm)
pbc             = xyz    ; 3D PBC

;----------------------------------------------------
; ELECTROSTATICS
;----------------------------------------------------
coulombtype      = PME      ; Particle Mesh Ewald for long-range electrostatics
rcoulomb         = 1.0      ; short-range electrostatic cutoff (in nm)
ewald_geometry   = 3d       ; Ewald sum is performed in all three dimensions
pme-order        = 6        ; interpolation order for PME (default is 4)
fourierspacing   = 0.10     ; grid spacing for FFT
ewald-rtol       = 1e-6     ; relative strength of the Ewald-shifted direct potential at rcoulomb

;----------------------------------------------------
; VDW
;----------------------------------------------------
vdw-type                = PME
rvdw                    = 1.0
vdw-modifier            = Potential-Shift
ewald-rtol-lj           = 1e-3
lj-pme-comb-rule        = Geometric
DispCorr                = EnerPres

;----------------------------------------------------
; TEMPERATURE & PRESSURE COUPL
;----------------------------------------------------
tc_grps          = System
tau_t            = 1.0
ref_t            = 300
pcoupl           = Parrinello-Rahman
pcoupltype       = isotropic            ; uniform scaling of box vectors
tau_p            = 2                    ; time constant (ps)
ref_p            = 1.0                  ; reference pressure (bar)
compressibility  = 4.5e-05              ; isothermal compressibility of water (bar^-1)

;----------------------------------------------------
; VELOCITY GENERATION
;----------------------------------------------------
gen_vel      = no       ; Velocity generation is off (if gen_vel is 'yes', continuation should be 'no')
gen_seed     = -1       ; Use random seed
gen_temp     = 300

;----------------------------------------------------
; FREE ENERGY CALCULATIONS
;----------------------------------------------------
free-energy              = yes
couple-moltype           = Protein_chain_B
couple-lambda0           = vdw-q
couple-lambda1           = none
couple-intramol          = yes
separate-dhdl-file       = yes
sc-alpha                 = 0.5
sc-power                 = 1
sc-sigma		             = 0.3
init-lambda-state        = 0
coul-lambdas             = 0.0 0.25 0.5 0.75 1.0 1.00 1.0 1.0 1.0 1.0 1.0 1.0 1.00 1.0 1.00 1.0 1.00 1.0 1.00 1.0
vdw-lambdas              = 0.0 0.00 0.0 0.00 0.0 0.05 0.1 0.2 0.3 0.4 0.5 0.6 0.65 0.7 0.75 0.8 0.85 0.9 0.95 1.0 
nstdhdl                  = 100
calc-lambda-neighbors    = -1



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