[gmx-users] Problem in Free Energy Calculations

[shagun krishna]

Hii Justin,

Thanks for the suggestion. When I am performing the ligand simulation in
water I am getting the following error in nvt equilibration:

Program mdrun, VERSION 4.6.5
Source code file: /build/buildd/gromacs-4.6.5/src/mdlib/domdec_top.c, line:
393

Fatal error:
56 of the 13118 bonded interactions could not be calculated because some
atoms involved moved further apart than the multi-body cut-off distance
(0.841804 nm) or the two-body cut-off distance (1.7 nm), see option -rdd,
for pairs and tabulated bonds also see option -ddcheck
For more information and tips for troubleshooting, please check the GROMACS
website at http://www.gromacs.org/Documentation/Errors

My nvt.mdp file is as follows:

; Run control
integrator               = sd       ; Langevin dynamics
tinit                    = 0
dt                       = 0.002
nsteps                   = 50000    ; 100 ps
nstcomm                  = 100
; Output control
nstxout                  = 500
nstvout                  = 500
nstfout                  = 0
nstlog                   = 500
nstenergy                = 500
nstxtcout                = 0
xtc-precision            = 1000
; Neighborsearching and short-range nonbonded interactions
nstlist                  = 10
ns_type                  = grid
pbc                      = xyz
rlist                    = 1.7
; Electrostatics
coulombtype              = PME
rcoulomb                 = 1.7
; van der Waals
vdw-type                 = switch
rvdw-switch              = 0.8
rvdw                     = 0.9
; Apply long range dispersion corrections for Energy and Pressure
DispCorr                  = EnerPres
; Spacing for the PME/PPPM FFT grid
fourierspacing           = 0.12
; EWALD/PME/PPPM parameters
pme_order                = 6
ewald_rtol               = 1e-06
epsilon_surface          = 0
optimize_fft             = no
; Temperature coupling
; tcoupl is implicitly handled by the sd integrator
tc_grps                  = system
tau_t                    = 1.0
ref_t                    = 300
; Pressure coupling is off for NVT
Pcoupl                   = No
tau_p                    = 0.5
compressibility          = 4.5e-05
ref_p                    = 1.0
; Free energy control stuff
free_energy              = yes
init_lambda              = 0.0
delta_lambda             = 0
foreign_lambda           = 0.05
sc-alpha                 = 0.5
sc-power                 = 1.0
sc-sigma                 = 0.3
couple-moltype           = 1M_R  ; name of moleculetype to decouple
couple-lambda0           = vdw      ; only van der Waals interactions
couple-lambda1           = none     ; turn off everything, in this case
only vdW
couple-intramol          = no
nstdhdl                  = 10
; Generate velocities to start
gen_vel                  = yes
gen_temp                 = 300
gen_seed                 = -1
; options for bonds
constraints              = h-bonds  ; we only have C-H bonds here
; Type of constraint algorithm
constraint-algorithm     = lincs
; Do not constrain the starting configuration
continuation             = no
; Highest order in the expansion of the constraint coupling matrix
lincs-order              = 12


On Mon, Jan 4, 2016 at 4:20 PM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 1/4/16 1:09 AM, shagun krishna wrote:
>
>> Hi Justin,
>> You mean to say that I don't need to follow your Free Energy Calculations
>> :
>> Methane in Water.
>> Actually I want to calculate the binding energy of my ligands with my
>> protein. All I should do is to run the one simulation of my ligands simply
>> in water and another is the protein-ligand complex simulation, both for
>> 10ns. I am really very confused because I have gone through literature and
>> all of them have calculated the value of α, β and  γ, which i guess can be
>> calculated by using free energy codes.
>>
>>
> I don't use the LIE algorithm, so I don't know all the details.  AFAIK
> these are empirical parameters to weight various contributions to the
> interaction energy.  LIE is ultimately an estimate of the free energy, and
> its accuracy depends on the quality of the fitted parameters.
>
> A rigorous free energy calculation is the best method for calculating free
> energy of binding.  For instance, LIE (again, AFAIK) relies solely on
> enthalpic terms, so it does not account for entropy unless you do
> additional work to figure this out separately.
>
>
> -Justin
>
> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
> ==================================================
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