[gmx-users] Protein Drug simulation Parameters

[tasneem kausar]

I have modified the trajectory running the trjconv command in three steps.
First trjconv is with -pbc whole, second is -pbc nojump with respect to
first frame and third is centering the the protein and drug. the output of
first step is provided as input in the second step and so on. When I am
calculating the RMSD of C-alpha atom for protein and C-alpha atom of
protein+drug their RMSD plot overlaps. However mmpbsa energy calculated
from this trajectory shows positive binding energy.
As RMSD plot of protein and protein+drug overlap suggests stable binding of
drug with protein then why the mmpbsa energy is positive and vice versa and
what is the reason behind it. I did not do -pbc cluster and -ur compact
with the trajectory as I am getting nice trajectory with these three option
on visualization.  Moreover I wish someone should give me some reading
materials on use of pbc options and its influence on binding energy.



On Tue, Sep 27, 2016 at 5:16 PM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 9/27/16 7:32 AM, tasneem kausar wrote:
>
>> Thank you Justin for your reply.
>> There is another question regarding MMPBSA energy calculations. I have
>> calculated the MMPBSA energy of 8 potential protein+drug complex.
>> Simulation time was 50 ns. One of the protein drug complex gives the
>> positive binding energy. Does the periodic boundary conditions like whole
>> and nojump effect the binding energy.
>>
>>
> Of course.  You need to provide sensible configurations to analyze.  If
> the trajectory is not imaged properly, the results will be nonsense.  But
> of course, it is simple to tell if the input trajectory is OK - watch it.
>
> -Justin
>
>
> On Mon, Sep 26, 2016 at 5:41 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>
>>
>>>
>>> On 9/26/16 4:43 AM, tasneem kausar wrote:
>>>
>>> Dear All
>>>>
>>>> I have performed MD simulation of protein and drug crystal structure. I
>>>> have generated drug  itp file from PRODRG server and corrected the
>>>> charges
>>>> of atoms as suggested in Justin's paper J. Chem. Inf. Model. 2010, 50,
>>>> 2221–2235.
>>>> I have done 50 ns MD simulation of protein and drug using g43a1 force
>>>> field
>>>> and spc water model. After 15 ns drug molecule comes out of the pocket.
>>>> Is this expected during MD simulation. If this occurs what is the reason
>>>> behind it.
>>>> Should we change any specific parameter for protein drug simulation.
>>>>
>>>>
>>>> First, make sure it is not a simple periodicity issue by re-imaging the
>>> trajectory with trjconv.  Several iterations will likely be necessary;
>>> see
>>> http://www.gromacs.org/Documentation/Terminology/Periodic_
>>> Boundary_Conditions#Suggested_trjconv_workflow
>>>
>>> If there is some legitimate problem that leads to ligand dissociation,
>>> either your run settings are inappropriate, the initial geometry has
>>> large
>>> clashes that lead to large forces that expel the ligand, or the ligand
>>> topology is incorrect and overly attracted to the bulk aqueous
>>> environment.
>>>
>>> -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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