[gmx-users] free energy

[Justin Lemkul]

On 4/26/15 8:54 AM, fatemeh ramezani wrote:
> Dear gmx-usersI want to calculate free energy of binding of ligand to Au surface in 8 ns simulation. I considered 7 lambda (lambda= 0, 0.2, 0.4, 0.6, 0.8, 0.9, 1) and for every lambda a mdp file. for example lambda-0 mdp file:
> title               =  n.pdb restraining
> cpp                 =  /lib/cpp
> constraints         =  all-bonds
> constraint_algorithm = lincs
> lincs_order         = 4
> lincs_iter          = 1
> integrator          =  sd
> dt                  =  0.0008
> nsteps              =  2500000
> nstcomm             =  100
> nstcalcenergy       =  100
> nstdhdl             =  100
> comm_mode           =
> nstxout             =  5000
> nstvout             =  5000
> nstfout             =  0
> nstlog              =  5000
> nstenergy           =  5000
> nstlist             =  10
> ns_type             =  grid
> rlist               =  1.4
> ;rlistlong           =  2
> coulombtype         =  PME
> rcoulomb            =  1.4
> rcoulomb-switch     =  0.8
> rvdw                =  1
> vdwtype             =  shift
> rvdw-switch         =  0.9
> fourierspacing      =  0.12
> fourier_nx          =  0
> fourier_ny          =  0
> fourier_nz          =  0
> pme_order           =  6
> ewald_rtol          =  1e-5
> optimize_fft        =  yes
>
> ; Berendsen temperature coupling is on in three groups
> Tcoupl              =  V-rescale
> tau_t               =  0.1       0.1
> tc-grps            =  Protein   Non-Protein
> ref_t               =  300       300
> ; Pressure coupling is  on
> ;Pcoupl              =  berendsen
> Pcoupl              =  Parrinello-Rahman
> Pcoupltype         =  isotropic
> tau_p               =  5
> compressibility     =  4.5e-5
> ref_p               =  1.0
> ; Generate velocites is on at 300 K.
> gen_vel             =  yes
> gen_temp            =  300.0
> gen_seed            =  173529
> energygrps          = Protein  Sol
> freezegrps          = AU  AUI       AUC
> freezedim           = Y Y Y  Y Y Y  Y Y Y
> free-energy         = yes
> couple-moltype      = Protein2
> init-lambda         = 0
> sc-power            = 1
> sc-sigma            = 0.3
> sc-alpha            = 1
> couple-intramol     =  no
> couple-lambda1      = vdwq
> couple-lambda0      = none
> foreign-lambda      = &ALL_LAMBDAS$
> As you can see dt= 0.0008, for 8 ns simulation, I should take the nstep of each Lambda 10000 ( or I should divide 8 ns  between 7  Lambda)? In other words, the simulation time for each of the 7 lambda should be 8 ns or every lambda simulation time should be considered so that the total simulation time of lambdas be 8 ns?

How have you predetermined that you want 8 ns total, split over 7 states?  You 
should do some test runs to assess convergence and determine how much sampling 
per state is necessary, rather than just assume a certain time.

-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

==================================================