[gmx-users] Topology parameters for ligand

Tue Jan 10 10:06:09 CET 2017

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.

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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