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

Wed Oct 10 03:06:23 CEST 2012

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://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/
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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

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