[gmx-users] Problem in Free Energy Calculations
shagun krishna
krishna.shagun123 at gmail.com
Tue Jan 5 07:34:35 CET 2016
Hi Justin..
Thanks a ton to you. Finally I have completed the simulation of ligand in
solvent. In your earlier mail you have written that to calculate the
binding energy of protein-ligand I will need the nonbonded interaction
energy between protein-ligand coming from protein-ligand simulation and the
ligand-water interaction energy coming from the second simulation. For
final ΔG binding I should substract these two energies, if I am not wrong.
PLs suggest me.
Thanx in advance..
Best regards,
SHAGUN
On Mon, Jan 4, 2016 at 4:58 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>
> On 1/4/16 6:25 AM, shagun krishna wrote:
>
>> 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
>>
>>
>
> http://www.gromacs.org/Documentation/Terminology/Blowing_Up#Diagnosing_an_Unstable_System
>
> Your ligand topology is probably incorrect in some way. Turn off the free
> energy code, use sensible cutoffs as required by the parent force field,
> and follow the above link.
>
> -Justin
>
>
> 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
>>>
>>> ==================================================
>>> --
>>> Gromacs Users mailing list
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>>>
> --
> ==================================================
>
> 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
>
> ==================================================
> --
> Gromacs Users mailing list
>
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