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

Justin Lemkul jalemkul at vt.edu
Wed Oct 10 03:24:18 CEST 2012 


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

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://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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>
>
>

-- 
========================================

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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