[gmx-users] Topology parameters for ligand

[tasneem kausar]

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.



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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