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

Liu Shiyong liushiyong at gmail.com
Wed Oct 10 03:17:50 CEST 2012 

Justin,

 Single mutation for four residue. The number of mutants is 4x19=76
Of course , that is a tiny peptide library.


Best

Shiyong

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://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
>
> ========================================
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-- 
Shiyong Liu
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Huazhong University of Science and Technology, Wuhan 430074, Hubei, China
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