[gmx-users] Topology parameters for ligand

[Justin Lemkul]

On 1/10/17 4:05 AM, tasneem kausar wrote:
> Thank You for your reply
>
> The system under my study has positive charge. There are 3 positive charges
> on the protein and one on drug molecule. How these charges will be handled.
>

Like any others.  A non-zero formal charge of a species does not preclude you 
from doing free energy calculations.

-Justin

>
> On Mon, Jan 9, 2017 at 6:37 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>>
>> On 1/9/17 2:31 AM, tasneem kausar wrote:
>>
>>> I got it.
>>>
>>> I have looked at the input files for the T4-lysozyme tutorial available at
>>> alchemistry.org. They have defined state A and state B. I am using
>>> GROMACS-5.1.4 for these calculation. So as mentioned in gromacs manual
>>> decoupling parameters are taken from the mdp options, like by defining
>>> [lambda-moltype] in mdp file. As I know from the tutorials and manual the
>>> solvation free energy of the ligand can calculated.
>>>
>>> From the alchemistry.org input files, the topology parameters of ligand
>>> are
>>> inserted in protein topology named as complex.top.
>>>
>>> If I follow the same protocol without defining the state B of the ligand
>>> in
>>> topology, how the ligand molecule will be decoulped in complex.
>>>
>>>
>> An explicit B-state is necessary for a relative free energy calculation,
>> in which one molecule is transformed into another.
>>
>> For any absolute free energy calculation (solvation, binding, etc) then
>> you do not need to define a B-state, and just couple the physical
>> parameters to lambda to turn them on/off.
>>
>> -Justin
>>
>>
>>
>>>
>>> On Sun, Jan 8, 2017 at 10:21 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>>
>>>
>>>>
>>>> On 1/7/17 10:29 PM, tasneem kausar wrote:
>>>>
>>>> Thank you for your reply
>>>>>
>>>>> In last section of your tutorial you have suggested some changes to made
>>>>> in
>>>>> mdp file. That can be used for solvation free energies.
>>>>> For free energy calculation of protein drug complex, is it only lambda
>>>>> restraint to be defined?
>>>>>
>>>>>
>>>>> Along with a complex system of [intermolecular_interactions] that
>>>> preserve
>>>> the relative orientation of the ligand.  This is a very complex
>>>> calculation
>>>> in practice.  See examples on alchemistry.org and in the literature in
>>>> works by Roux, Im, Karplus, etc.  My tutorial is not very useful for such
>>>> calculations; it is extremely basic relative to what is needed to carry
>>>> out
>>>> a binding free energy calculation.  I only mentioned it there because so
>>>> many people asked about it and I wanted to clear up any confusion.
>>>>
>>>> -Justin
>>>>
>>>>
>>>> On 8 Jan 2017 01:45, "Justin Lemkul" <jalemkul at vt.edu> wrote:
>>>>
>>>>>
>>>>>
>>>>>
>>>>>> On 1/7/17 6:05 AM, tasneem kausar wrote:
>>>>>>
>>>>>> Dear all
>>>>>>
>>>>>>>
>>>>>>> I am following Justin's tutorial methane in water for free energy
>>>>>>> calculation. I am using Gromacs-5.1.4. The charges of methane in
>>>>>>> topology
>>>>>>> are set to zero. So following the same protocol, is it relevant to set
>>>>>>> the
>>>>>>> charges at zero in topology of the drug. I am confused because in
>>>>>>> tutorial
>>>>>>> of Sander (ethanol in water) charges are present in the topology file.
>>>>>>>
>>>>>>> Please tell me the difference in both the tutorials and how can I
>>>>>>> apply
>>>>>>> it
>>>>>>> to drug that I want to study.
>>>>>>>
>>>>>>>
>>>>>>> The charges in my tutorial are set to zero because the stated goal of
>>>>>>>
>>>>>> that
>>>>>> tutorial is to reproduce *only the LJ portion of the hydration free
>>>>>> energy*
>>>>>> to match a published paper.  This creates a very simple, robust system.
>>>>>> If
>>>>>> you want to calculate a real, meaningful hydration or binding free
>>>>>> energy,
>>>>>> charge transformation is required.
>>>>>>
>>>>>> -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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>>>> 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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>> 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

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