From: James Starlight (jmsstarlight_at_gmail.com)
Date: Wed Jul 23 2014 - 15:32:53 CDT
Hi Thomas,
this is some receptor from the GPCR family but with no known experimental
structure available at this moment. The reason of the refirement of the
extracellular loops is that I need very good model for further md
simulation to study initial ligand binding (which happens initially in
these extracellular loops) with the receptor (like in this paper
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156183/ ). In case of this
receptor modeller never predicted some secondary structure elements in the
region of second extracellular loop (which always looks like very long coil
(~30 aa) althought 2 disulphide bridges are located here as the possible
constraints) although we changes templates (in other GPCRs for instance in
Beta-adrenergic receptor) there are short helix in this region for instance
which is the vestibule to the ligand-binding pocket.
On other hand we never do *MANY* models. From your suggestion it seems that
I need to generate many models (e.g 1000 pdbs) which will be with the same
bundle but differ only in one extracellular loopin which I most interested.
Than I need to cluster my 1000 pdbs according to the conformation of
extracellulalar loop and chose some shared conformation which will be in
most populated cluster. Could you provide me with the ideas of some soft
which will be good for this which will have i)python interface ii) tutorial
:-)?
Many thanks for suggestions,
James
2014-07-24 0:02 GMT+04:00 Thomas Evangelidis <tevang3_at_gmail.com>:
>
>
>
> On 23 July 2014 22:24, James Starlight <jmsstarlight_at_gmail.com> wrote:
>
>> Dear NAMD users,
>> I'm very appologise, this question was adressed to both forums :-)
>> My question is refirement of loops predicted by modeller
>> the goal is
>> 1- just refine loops but not refine rest of the protein (freezing it)
>> 2- avoid to use the membrane, because I'd like to refine water expoised
>> regions of the membrane protein only
>> 3- enhansing sampling engine to refine it quickly
>> 4- do several refirement simulation, use PCA to test coverage (found
>> shared regions in PC projections of the loops conformations predicted by
>> such refirement from seveal simulations)
>>
>>
> Do you realize how much time this protocol needs to reach convergence on
> the eigenvectors of the accumulated trajectory (if that ever happens at
> all)? Why not just create tens of thousands of loop models, cluster them
> and start a simulation from the representative conformation of the
> predominant cluster?
>
> On another note, are these extracellular and intracellular loops so
> important to invest that amount of labour on them? What kind of protein is
> this? Can you upload some pictures on Dropbox to show us the protein with
> the loops coloured differently?
>
>
>
>> 2014-07-23 23:14 GMT+04:00 Pino, James Christopher <
>> james.c.pino_at_vanderbilt.edu>:
>>
>>> Your greeting implies this went to the wrong forum.
>>>
>>> However, I am using aMD through amber also.
>>>
>>> I am curious what your goal is? Loop refinement of de novo models?
>>>
>>>
>>> James
>>> Vanderbilt University
>>>
>>> ________________________________________
>>> From: owner-namd-l_at_ks.uiuc.edu [owner-namd-l_at_ks.uiuc.edu] on behalf of
>>> James Starlight [jmsstarlight_at_gmail.com]
>>> Sent: Wednesday, July 23, 2014 6:30 AM
>>> To: Namd Mailing List
>>> Subject: [External] namd-l: Boost value in aMD simulation
>>>
>>>
>>> Dear Amber users!
>>>
>>> In this topic I would like to talk about information obtained from the
>>> amd.log concerning the reasonability of the values of boost potentials
>>> applied to my system. For my case I'm simulating protein in explicit water
>>> with the task to refine its loops appling position restraints on part of
>>> the protein (which I'd like to keep unchanged). Firstly I've performed cMD
>>> with no restraints to obtain all values needed to compute boost and alpha
>>> according to the impirical formuli presented in manual. Then I run 2 boost
>>> aMD with applied of the position restraints on the bigger part of the
>>> protein and see amd.log. According to themd.log the value of dihedral
>>> boost added to my system per step during amd simulation has been ~ 10
>>> Kcal/mol on each step. I wounder if the dihe boost of this value have been
>>> applied to the whole protein (including its restrained parts) or only to
>>> its unrestrained (in my case loops) parts? What the reasonable dUdihe
>>> should be expected in principle for the simulation of protein consisted of
>>> ~ 300 amino acids? I guess that this value should be nuch biger than
>>> several Kcal/ mol to obtain better sampling.
>>>
>>>
>>>
>>>
>>> Thanks for suggestions,
>>>
>>>
>>> James
>>>
>>
>>
>
>
> --
>
> ======================================================================
>
> 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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