[gmx-users] Using the md integrator for calculating free energy of solvation
Dan Gil
dan.gil9973 at gmail.com
Tue May 2 22:44:09 CEST 2017
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
>>>
>>> ==================================================
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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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