[gmx-users] Regarding value of Elj, Eqq, Clj and Cqq values using LIE Approach

Thu Jan 7 14:26:24 CET 2016

On 1/7/16 1:46 AM, shagun krishna wrote:
> Hiii Justin,
>
> Thanks again for replying to my query. I just wanted to know your opinion
> that while performing ligand alone simulation in water, is it correct to
> just take the .mdp files from lysozyme tutorial and change accordingly
> without changing any parameters like Bond parameter,Neighborsearching,
> Electrostatics, Temperature coupling and pressure coupling. Or can we take
> these setting (except md; because in md.mdp it is using sd integrator, how
> ever in all other settings it is using md integrator) from the Solvation
> free energy of ethanol tutorial by Sander Pronk
>

The Langevin integrator is preferred for free energy calculations because of 
better sampling.  For simple interaction energy calculations, you can probably 
use any integrator you like.

The remaining settings largely depend on the force field being used, especially 
the nonbonded options.  Getting these right is critical.  The lysozyme tutorial 
has settings generally found in the literature for OPLS-AA simulations of 
proteins.  If you are using any other force field, you need to make 
corresponding corrections.  Use of constraints may depend on the force field, as 
well.

> I am using nvery expensive settings, I guess that this may be a probable
> reason for getting higher values of Elj and Eqq. Kindly let me know that
> from where should I select a the .mdp setting for simulation of ligand in
> water only, without going through free energy codes.
>

What do you mean "expensive settings?"  What is your ligand and how have you 
parametrized and validated it?  A poor ligand topology will lead to completely 
useless results...

-Justin

> Thanks in advance.
>
> Regards,
>
> Shagun
>
> On Wed, Jan 6, 2016 at 11:27 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>>
>> On 1/6/16 12:52 PM, shagun krishna wrote:
>>
>>> Thanks for your reply Justin. I know it well that your that tutorial is
>>> nothing to do with g_lie. But being as a gromacs user I am not getting
>>> this
>>> point so I am asking this question.
>>>
>>
>> I was pointing it out for clarity in the archive only; I know you
>> understand this point, but when someone types in the right words to Google,
>> they may get seriously confused by what they see :)
>>
>> For the protein I am taking all the default values which has been set by
>>> g_lie program. And for the ligand we have to calculate it using g_energy
>>> module. I have done with that part also. But f*or my ligand I am obtaining
>>> Elj (LJ-14)= 226.365 and Eqq (*Coulomb-14) *= -125.048 (both in KJ/mol).**
>>> When I am comparing them with their respective counterpart for the protein
>>> (Clj and Cqq value 0.181 and 0.5 respectively; the Elj and Eqq values are
>>> set 0 for the protein), they seem to be very large. Is it natural or there
>>> is something wrong in my procedure. *
>>>
>>
>> 1-4 interactions are intramolecular terms. These are not what you want.
>>
>> You need:
>>
>> (1) Protein-ligand interaction energy (from energygrps = Protein LIG) in
>> the complex simulation. You pass this .edr file to gmx lie.  Of course, if
>> water plays any role in the interaction of the protein, or it is partially
>> hydrated in the binding site, the result you get will not be right.
>> (2) Ligand-water interaction energy (from energygrps = LIG SOL) from a
>> simulation of the ligand in water. You pass these values to -Eqq and -Elj
>> to gmx lie.
>>
>> As for the -Clj and -Cqq values, I still don't know.  Hopefully someone
>> who does will chime in with something useful.  But again, the primary
>> literature (and there are a number of LIE papers, I'm just not well-versed
>> in their details) should tell you everything you need.
>>
>> -Justin
>>
>> *PS I have performed simple gromacs simulation of ligand in water (that has
>>> not included your free energy codes).*
>>>
>>> *Regards*
>>>
>>> *Shagun*
>>>
>>>
>>> On Wed, Jan 6, 2016 at 9:42 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>>
>>>
>>>>
>>>> On 1/6/16 1:20 AM, shagun krishna wrote:
>>>>
>>>> Dear Gmx-user,
>>>>>
>>>>> I am using LIE approach to calculate the binding energy of my protein
>>>>> and
>>>>> ligand. When I am running g_lie program for my protein I am getting the
>>>>> value of DeltaG= 0. Can you please suggest me a way to get the values of
>>>>> Elj, Eqq, Clj and Cqq and also about the post-processing necessary to
>>>>> run
>>>>> a
>>>>> LIE calculation. It is not given in tutorial. I have ran two separate
>>>>> simulations: one for receptor-ligand complex and another for ligand
>>>>> alone
>>>>> in solvent.  I am following Justin tutorial for free energy calculation.
>>>>>
>>>>>
>>>>> For the sake of clarity in the archive, I again reiterate that my free
>>>> energy tutorial has nothing to do with LIE.
>>>>
>>>> The values of Elj and Eqq are what you get from simulating the ligand in
>>>> water with appropriate energygrps.
>>>>
>>>> The values of Clj and Cqq are the parameters you have to figure out.
>>>> What
>>>> do the papers on LIE say?  There are defaults given in gmx lie, where do
>>>> they come from?
>>>>
>>>> -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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>> --
>> ==================================================
>>
>> 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

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