[gmx-users] Using the md integrator for calculating free energy of solvation
Dan Gil
dan.gil9973 at gmail.com
Wed May 3 16:43:32 CEST 2017
Hi Dr. Kausar,
If I want the molecule to have all of its nonbonded interactions with the
rest of the system (solvent) at each lambda, don't I want to have vdwq
option ON for both couple-lambda0 and couple-lambda1?
What I am attempting to do is mutate molecule A to molecule B through the
simulation.
Best Regards,
Dan
On Wed, May 3, 2017 at 1:04 AM, Tasneem Kausar <tasneemkausar12 at gmail.com>
wrote:
> In the last line of mdp file couple-lambda0 and couple-lambda1 have the
> same vdwq variable. It indicates A and B state of system. So grompp is
> complaining about the identical states.
>
> You can also see the alchemistry.org for detail information about the free
> energy calculations.
>
> On Wed, May 3, 2017 at 2:14 AM, Dan Gil <dan.gil9973 at gmail.com> wrote:
>
> > Thank you Dr. Lemkul,
> >
> > Following your advice, I was able to calculate the solvation free energy
> of
> > two molecules that I am interested in. The results, unfortunately, were
> not
> > what I expected. I want to try an alternative method, that is, the
> > alchemical thermodynamic integration method.
> >
> > If I understand this correctly, I should be able to calculate the free
> > energy difference between two systems A and B as I change the topology of
> > the molecule from A to B in small steps.
> >
> > I wasn't able to find a tutorial online, but I attempted to try the
> method
> > and I obtained this error from grompp:
> >
> > WARNING 1 [file grompp.mdp, line 43]:
> > The lambda=0 and lambda=1 states for coupling are identical
> >
> > I was hoping if you could help me understand what I am missing in my
> > topology or mdp file.
> >
> > Topology:
> > [ moleculetype ]
> > HEPT 3
> >
> > [ atoms ]
> > 1 opls_135 1 HEPT CH3 1 -0.180 12.011
> > opls_961 0.360 12.011
> > 2 opls_136 1 HEPT CH2 2 -0.120 12.011
> > opls_962 0.240 12.011
> > 3 opls_136 1 HEPT CH2 3 -0.120 12.011
> > opls_962 0.240 12.011
> > 4 opls_136 1 HEPT CH2 4 -0.120 12.011
> > opls_962 0.240 12.011
> > 5 opls_136 1 HEPT CH2 5 -0.120 12.011
> > opls_962 0.240 12.011
> > 6 opls_136 1 HEPT CH2 6 -0.120 12.011
> > opls_962 0.240 12.011
> > 7 opls_135 1 HEPT CH3 7 -0.180 12.011
> > opls_961 0.360 12.011
> > 8 opls_140 1 HEPT H 1 0.060 1.008
> > opls_965 -0.120 18.998
> > 9 opls_140 1 HEPT H 1 0.060 1.008
> > opls_965 -0.120 18.998
> > 10 opls_140 1 HEPT H 1 0.060 1.008
> > opls_965 -0.120 18.998
> > 11 opls_140 1 HEPT H 2 0.060 1.008
> > opls_965 -0.120 18.998
> > 12 opls_140 1 HEPT H 2 0.060 1.008
> > opls_965 -0.120 18.998
> > 13 opls_140 1 HEPT H 3 0.060 1.008
> > opls_965 -0.120 18.998
> > 14 opls_140 1 HEPT H 3 0.060 1.008
> > opls_965 -0.120 18.998
> > 15 opls_140 1 HEPT H 4 0.060 1.008
> > opls_965 -0.120 18.998
> > 16 opls_140 1 HEPT H 4 0.060 1.008
> > opls_965 -0.120 18.998
> > 17 opls_140 1 HEPT H 5 0.060 1.008
> > opls_965 -0.120 18.998
> > 18 opls_140 1 HEPT H 5 0.060 1.008
> > opls_965 -0.120 18.998
> > 19 opls_140 1 HEPT H 6 0.060 1.008
> > opls_965 -0.120 18.998
> > 20 opls_140 1 HEPT H 6 0.060 1.008
> > opls_965 -0.120 18.998
> > 21 opls_140 1 HEPT H 7 0.060 1.008
> > opls_965 -0.120 18.998
> > 22 opls_140 1 HEPT H 7 0.060 1.008
> > opls_965 -0.120 18.998
> > 23 opls_140 1 HEPT H 7 0.060 1.008
> > opls_965 -0.120 18.998
> > ... And so on with the bonds, pairs, angles, and dihedrals directive.
> >
> > MDP File:
> >
> > ;Integration Method and Parameters
> > integrator = md
> > nsteps = 10000
> > dt = 0.002
> > nstenergy = 1000
> > nstlog = 5000
> >
> > ;Output Control
> > nstxout = 0
> > nstvout = 0
> >
> > ;Cutoff Schemes
> > cutoff-scheme = group
> > rlist = 1.0
> > vdw-type = cut-off
> > rvdw = 2.0
> >
> > ;Coulomb interactions
> > coulombtype = pme
> > rcoulomb = 1.0
> > fourierspacing = 0.4
> >
> > ;Constraints
> > constraints = all-bonds
> >
> > ;Temperature coupling
> > tcoupl = v-rescale
> > tc-grps = system
> > tau-t = 0.1
> > ref-t = 300
> >
> > ;Pressure coupling
> > pcoupl = parrinello-rahman
> > ref-p = 1.01325
> > compressibility = 4.5e-5
> > tau-p = 5
> >
> > ;Free energy calculation
> > free-energy = yes
> > init-lambda = 0
> > delta-lambda = 0.00001
> > couple-moltype = HEPT
> > couple-lambda0 = vdwq
> > couple-lambda1 = vdwq
> >
> > On Mon, Apr 3, 2017 at 2:05 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
> >
> > >
> > >
> > > On 4/3/17 2:01 PM, Dan Gil wrote:
> > >
> > >> Thank you Dr. Lemkul,
> > >>
> > >> I am trying to run grompp with the md integrator, but I am getting
> this
> > >> error:
> > >> "For proper sampling of the (nearly) decoupled state, stochastic
> > dynamics
> > >> should be used"
> > >>
> > >> Should I ignore this warning with the -maxwarn option and try running
> > it?
> > >> I
> > >> will see if I obtain comparable values for ethanol.
> > >>
> > >>
> > > People have already done such a comparison and that's why grompp is
> > > telling you this - it's better to use the Langevin integrator. You'll
> > get
> > > better sampling, particularly towards the end states. Using -maxwarn
> > tells
> > > grompp "you're trying to prevent me from making a mistake, but I want
> to
> > do
> > > it anyway" :) You'd better have a really, really good reason to try to
> > > override it.
> > >
> > > -Justin
> > >
> > >
> > > Best Regards,
> > >>
> > >> Dan
> > >>
> > >>
> > >> On Mon, Mar 27, 2017 at 12:51 PM, Justin Lemkul <jalemkul at vt.edu>
> > wrote:
> > >>
> > >>
> > >>>
> > >>> On 3/26/17 9:40 PM, Dan Gil wrote:
> > >>>
> > >>> Hi,
> > >>>>
> > >>>> I am following Dr. Sander Pronk's and Dr. Justin Lemkul's tutorial
> on
> > >>>> calculating free energy of solvation. Is it possible and
> theoretically
> > >>>> sound to use the md integrator instead of the sd integrator for
> these
> > >>>> calculations?
> > >>>>
> > >>>>
> > >>>> Langevin dynamics gives better sampling so it is frequently used for
> > >>> free
> > >>> energy calculations. You may get comparable results with the
> leap-frog
> > >>> integrator, but I haven never done a side-by-side comparison.
> > >>>
> > >>> -Justin
> > >>>
> > >>> I have already done a considerable amount of work using md
> integration,
> > >>> and
> > >>>
> > >>>> I want to make sure that the free energy values I calculate are
> > >>>> consistent
> > >>>> with my previous work.
> > >>>>
> > >>>> If using the md integrator is not sound, is there an alternative way
> > of
> > >>>> calculating solvation energy that will be consistent?
> > >>>>
> > >>>> Best Regards,
> > >>>>
> > >>>> Dan
> > >>>>
> > >>>>
> > >>>> --
> > >>> ==================================================
> > >>>
> > >>> 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
> > >
> > > ==================================================
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