[gmx-users] Interaction study for peptide-receptor..

rama david ramadavidgroup at gmail.com
Wed Oct 10 05:47:03 CEST 2012 

Hi,

Yes it is possible to screen peptides as ligand.

But for these following information is needed

1.  Binding site of peptide and ligand
 2. Which residues in peptide are important for binding.

After you simply do the mutation on the desired peptide.Performed the MD
upto 50 ns

Find the interaction energy.

As the MD need a lot of time , you can´t use it for the large library.
I plan to do only 5 simulation.


With best wishes and regards.
Rama david




On Wed, Oct 10, 2012 at 6:54 AM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 10/9/12 9:17 PM, Liu Shiyong wrote:
>
>> Justin,
>>
>>   Single mutation for four residue. The number of mutants is 4x19=76
>> Of course , that is a tiny peptide library.
>>
>>
> Of course one can design many different mutants with a 4-residue peptide
> (far more than 76 in fact, considering all possible combinations of all 20
> amino acids), but I do not believe that is the intent of the OP here.
>  Referring to the original post:
>
> http://lists.gromacs.org/**pipermail/gmx-users/2012-**October/075182.html<http://lists.gromacs.org/pipermail/gmx-users/2012-October/075182.html>
>
> It seems that 4 total simulations are intended (perhaps 4 simulations with
> replicates).
>
> -Justin
>
>
>  On Wed, Oct 10, 2012 at 9:06 AM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>
>>>
>>>
>>> On 10/9/12 8:43 PM, Liu Shiyong wrote:
>>>
>>>>
>>>> Hi,
>>>>
>>>> Your expectation from MD is too much than reality.
>>>>
>>>> Peptide design is an open problem. Lots of elegant protocols are
>>>> available. However, to my understanding, the core problem is still
>>>> about protein-peptide docking and scoring. MD simulation only helps on
>>>> some special cases. It is impossible that MD simulation is used to for
>>>> screening peptide library.
>>>>
>>>>
>>> I would hardly call 4 different mutants a library.  Plenty of methods
>>> exist
>>> to enhance the sampling of such systems and have been used to great
>>> effect.
>>> Computationally expensive to pull off properly?  Yes.  Impossible?  In
>>> this
>>> case, I would say no.
>>>
>>> -Justin
>>>
>>>
>>>
>>>> On Thu, Oct 4, 2012 at 9:16 PM, rama david <ramadavidgroup at gmail.com>
>>>> wrote:
>>>>
>>>>>
>>>>> Thank you  for reply,
>>>>>    I read the recently published article in Biochemistry.
>>>>> They worked on the same receptor that I am working.
>>>>> ( as I mention in my previous mail)
>>>>> They used NAMD software and I am using gromacs.
>>>>> They sliced the  receptor binding site and used the the solid support
>>>>> to the binding site and did simulation.
>>>>>                  So if I freeze  the group is it will ok ??
>>>>> Is it possible in gromacs to fix the residue on solid immobilized
>>>>> surface.
>>>>> If it is how to do it??
>>>>>
>>>>> my question is How to decide which group are remove and which group
>>>>> should
>>>>> keep in simulation.????
>>>>>
>>>>> thank you in advance
>>>>> Thank you for giving your valuable time and advice to me.
>>>>>
>>>>> With best wishes and regards,
>>>>> Rama david
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>> On Thu, Oct 4, 2012 at 6:11 PM, Thomas Evangelidis
>>>>> <tevang3 at gmail.com>wrote:
>>>>>
>>>>>  I don't think AutoDock and Vina are suitable for peptide docking. I
>>>>>> would
>>>>>> first try the FlexPepDocking module of Rosetta which does ab initio
>>>>>> folding
>>>>>> of the peptide on the receptor, while moving the side-chains of the
>>>>>> protein
>>>>>> but leaves its backbone intact. Rosetta implements a knowledge-based
>>>>>> scoring, which has been specifically designed for this task and is as
>>>>>> fast
>>>>>> as Vina or AutoDock.
>>>>>>
>>>>>> I would first do that and if I wouldn't get any reasonable results
>>>>>> then
>>>>>> I
>>>>>> would move to MD starting from the top scored protein-peptide
>>>>>> complexes
>>>>>> created by Rosetta.
>>>>>>
>>>>>> Thomas
>>>>>>
>>>>>>
>>>>>> On 4 October 2012 15:08, rama david <ramadavidgroup at gmail.com> wrote:
>>>>>>
>>>>>>  Hi francesco,
>>>>>>>
>>>>>>> Thank you For reply.
>>>>>>> I did docking but the result are not so impressive.
>>>>>>> I used vina and autodock.
>>>>>>> I also did virtual screening in autodock but the result are not upto
>>>>>>> the
>>>>>>> mark.
>>>>>>>
>>>>>>> Is the freezing of group can affect my system?? How much efficiency I
>>>>>>> get
>>>>>>> by these work??
>>>>>>> As these group are going to freeze in four simulation so if it affect
>>>>>>> one
>>>>>>> ligand it  affect other
>>>>>>> ligand also.
>>>>>>>
>>>>>>> I read article that did the work like me ,
>>>>>>> they sliced the binding residues and  used the inert solid sphere to
>>>>>>> support binding residues
>>>>>>> instead of the freezing group other group.
>>>>>>>
>>>>>>> I think both way should have same effect..Am I right or wrong??
>>>>>>>
>>>>>>> If you have any other way please suggest it..
>>>>>>>
>>>>>>> With best wishes and regards
>>>>>>> Rama david
>>>>>>>
>>>>>>>
>>>>>>> On Thu, Oct 4, 2012 at 5:07 PM, francesco oteri
>>>>>>> <francesco.oteri at gmail.com>**wrote:
>>>>>>>
>>>>>>>  Hi,
>>>>>>>> as far as I know, freezing just set velocities to 0 so you gain
>>>>>>>> nothing
>>>>>>>> freezing atoms.
>>>>>>>>
>>>>>>>> By the way, have you tried docking? It takes into account multiple
>>>>>>>> conformation and
>>>>>>>> orientation of the peptide and, depending upon the implemented
>>>>>>>>
>>>>>>>
>>>>>> algorithm,
>>>>>>
>>>>>>>
>>>>>>>> also
>>>>>>>> protein sidechain orientation.
>>>>>>>>
>>>>>>>> Francesco
>>>>>>>>
>>>>>>>>
>>>>>>>> 2012/10/4 rama david <ramadavidgroup at gmail.com>
>>>>>>>>
>>>>>>>>  thank you Justin for reply.
>>>>>>>>>
>>>>>>>>> I dont know about long range interactions.
>>>>>>>>> But as I freeze the group I think it will improve my computational
>>>>>>>>>
>>>>>>>>
>>>>>>> speed.
>>>>>>>
>>>>>>>>
>>>>>>>>> So is there any way to find out or decide which group should be
>>>>>>>>> freeze, and which group should affect my interaction most
>>>>>>>>> probably??
>>>>>>>>>
>>>>>>>>> Should I do Essential Dynamics ??? or Principle component analysis
>>>>>>>>>
>>>>>>>>
>>>>>> ???
>>>>>>
>>>>>>>
>>>>>>>>>
>>>>>>>>> Would you suggest me any general protocol for such work??
>>>>>>>>>
>>>>>>>>> Thank you in Advance
>>>>>>>>>
>>>>>>>>>
>>>>>>>>> With Best Wishes and regards.
>>>>>>>>> Rama David
>>>>>>>>>
>>>>>>>>> On Thu, Oct 4, 2012 at 3:57 PM, Justin Lemkul <jalemkul at vt.edu>
>>>>>>>>>
>>>>>>>>
>>>>>> wrote:
>>>>>>
>>>>>>>
>>>>>>>>>
>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>> On 10/4/12 2:01 AM, rama david wrote:
>>>>>>>>>>
>>>>>>>>>>  Hi gromacs Friends,
>>>>>>>>>>>                I want to do peptide-receptor ( Protein)
>>>>>>>>>>> interaction
>>>>>>>>>>> study.Receptor consist a single chain.
>>>>>>>>>>> Peptide is made up  of  4 amino acids. I know the interaction
>>>>>>>>>>>
>>>>>>>>>>
>>>>>>> pattern
>>>>>>>
>>>>>>>>
>>>>>>>> of
>>>>>>>>
>>>>>>>>>
>>>>>>>>>>> peptide and receptor.
>>>>>>>>>>> I plan to mutate single residue each at a time and  run 4
>>>>>>>>>>>
>>>>>>>>>>
>>>>>>> simulation .
>>>>>>>
>>>>>>>>
>>>>>>>>>>> So I will have the 4 different simulation that contain the
>>>>>>>>>>> mutated
>>>>>>>>>>> residues
>>>>>>>>>>> and the wild one.
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>> Then afterward from the interaction energy I want to select the
>>>>>>>>>>>
>>>>>>>>>>
>>>>>>>> peptide
>>>>>>>>
>>>>>>>>>
>>>>>>>>>>> which is showing
>>>>>>>>>>> stronger interaction than others.
>>>>>>>>>>>
>>>>>>>>>>> As  mention I know the binding site, If I freeze the remaining
>>>>>>>>>>>
>>>>>>>>>>
>>>>>>> portion
>>>>>>>
>>>>>>>>
>>>>>>>>> in
>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>> receptor
>>>>>>>>>>> that not involved in binding , Is it going to affect my screening
>>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>> process
>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>> ???
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>  Potentially.  Do you know that the binding interactions and the
>>>>>>>>>>
>>>>>>>>>
>>>>>>>> mutations
>>>>>>>>
>>>>>>>>>
>>>>>>>>>> will only perturb local residues?  Do you know that there are no
>>>>>>>>>>
>>>>>>>>>
>>>>>>>>> long-range
>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>> motions to be considered?
>>>>>>>>>>
>>>>>>>>>> I think you gain very little by freezing portions of the system,
>>>>>>>>>>
>>>>>>>>>
>>>>>> and
>>>>>>
>>>>>>>
>>>>>>>> risk
>>>>>>>>
>>>>>>>>>
>>>>>>>>>> more than you gain.
>>>>>>>>>>
>>>>>>>>>> -Justin
>>>>>>>>>>
>>>>>>>>>> --
>>>>>>>>>> ==============================****==========
>>>>>>>>>>
>>>>>>>>>> Justin A. Lemkul, Ph.D.
>>>>>>>>>> Research Scientist
>>>>>>>>>> Department of Biochemistry
>>>>>>>>>> Virginia Tech
>>>>>>>>>> Blacksburg, VA
>>>>>>>>>> jalemkul[at]vt.edu | (540) 231-9080
>>>>>>>>>> http://www.bevanlab.biochem.****vt.edu/Pages/Personal/justin<http://vt.edu/Pages/Personal/justin>
>>>>>>>>>> <
>>>>>>>>>>
>>>>>>>>>
>>>>>>>>> http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin<http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>
>>>>>>>>> >
>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>> ==============================****==========
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>>>>>>>> --
>>>>>>>> Cordiali saluti, Dr.Oteri Francesco
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>>>>>>>
>>>>>>
>>>>>>
>>>>>> --
>>>>>>
>>>>>> ==============================**==============================**
>>>>>> ==========
>>>>>>
>>>>>> Thomas Evangelidis
>>>>>>
>>>>>> PhD student
>>>>>> University of Athens
>>>>>> Faculty of Pharmacy
>>>>>> Department of Pharmaceutical Chemistry
>>>>>> Panepistimioupoli-Zografou
>>>>>> 157 71 Athens
>>>>>> GREECE
>>>>>>
>>>>>> email: tevang at pharm.uoa.gr
>>>>>>
>>>>>>             tevang3 at gmail.com
>>>>>>
>>>>>>
>>>>>> website: https://sites.google.com/site/**thomasevangelidishomepage/<https://sites.google.com/site/thomasevangelidishomepage/>
>>>>>> --
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>>>>
>>>>
>>>>
>>>>
>>>>
>>> --
>>> ==============================**==========
>>>
>>>
>>> Justin A. Lemkul, Ph.D.
>>> Research Scientist
>>> Department of Biochemistry
>>> Virginia Tech
>>> Blacksburg, VA
>>> jalemkul[at]vt.edu | (540) 231-9080
>>> http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin<http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>
>>>
>>> ==============================**==========
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>>
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>>
>>
> --
> ==============================**==========
>
> Justin A. Lemkul, Ph.D.
> Research Scientist
> Department of Biochemistry
> Virginia Tech
> Blacksburg, VA
> jalemkul[at]vt.edu | (540) 231-9080
> http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin<http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>
>
> ==============================**==========
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