Re: [External] Boost value in aMD simulation

From: James Starlight (jmsstarlight_at_gmail.com)
Date: Mon Aug 18 2014 - 03:25:53 CDT

Some additional question about to test convergence of my trajectories in
case of loop refirement:

e.g I have 10 trajectories calculated for the same system initiated from
different started velocities and with slightly different aMD boost values.
What might be better:

1) Merge all trajectories into 1 big trajectory and perform i) cluster
analysis to determine shared clusters in the selected refined (loop)
region= > test onto the structural convergence ii) PCA of this big
trajectory => determine shared modes of the collective motions seen in all
10 trajectories => test onto the dynamical convergence

Might it be useful?

James

2014-07-24 14:13 GMT+04:00 Thomas Evangelidis <tevang3_at_gmail.com>:

>
>
>
> On 24 July 2014 12:54, James Starlight <jmsstarlight_at_gmail.com> wrote:
>
>> Thanks again, Thomas!
>>
>> I guess that the combination of steered and accelerated MD could be very
>> effective method to monitor pathway of the ligand motion from the water
>> exteriour to the receptor orthosteric-binding pocket interiour (what is
>> exactly my goal at this moment!).
>>
>> Some techniqual questions:
>>
>> 1) could the averaged structure from the largest cluster be assumed as
>> the representative structure?
>>
>>
> I didn't mention the word "averaged", I mention the cluster
> representative. The answer is no. It may not be native like at all
> -especially for a loop of 30 aa-, but it's the closest you can get with the
> current computational tools.
>
>
>> 2) I guess that processing of 1 trajectory made from seveal tens of pdbs
>> by means of some md tools (e.g I coould look at amber processing besides
>> the gromacs tools) is good sollution. Do you know some software for
>> conversion of multi pdb to amber-like or gromacs-like trajectories ? In
>> past I've made only NMR-like format pdb from multi single pdbs.
>>
>>
> VMD.
>
>
>> Best,
>>
>> James
>>
>>
>>
>>
>> 2014-07-24 13:05 GMT+04:00 Thomas Evangelidis <tevang3_at_gmail.com>:
>>
>>
>>>
>>>
>>> On 24 July 2014 09:13, James Starlight <jmsstarlight_at_gmail.com> wrote:
>>>
>>>> Thomas, many thanks for the suggestion!
>>>>
>>>> So Rosetta in comparison to modeller could be used for i) prediction of
>>>> ss eleents in *long* loops ii) performing clustering of generated models
>>>> based on chosen criterium (e.g conformation of loop, or % of SS in its),
>>>> couldn't it?
>>>>
>>>> Bare in mind that you can restrain the secondary structure of the
>>> vestibule to helix with both software. As for clustering, I usually convert
>>> the models (.pdb files) to a trajectory and do the clustering with normal
>>> MD analysis tools (e.g. g_cluster). But there is also a stand-alone
>>> application named calibur that can read and cluster the pdb files directly.
>>>
>>>
>>>
>>>> Regarding the general workflow of the modelling and refirement based on
>>>> your assumptions I guess it would be more correct to do:
>>>>
>>>> 1) homology modelling by modeller/posetta-> clustering -> selection of
>>>> model from bigeest cluster
>>>>
>>>> selection of the representative structure of the largest cluster.
>>>
>>>
>>>> 2) short cmd simulation in membrane to relax the system
>>>>
>>>>
>>> By all means!
>>>
>>>
>>>> 3)loop refirement w/o membrane with applied position restraints (yes, I
>>>> dont like to kill this idea :-) )
>>>>
>>>>
>>> I doubt about the necessity of this step. I would proceed directly to
>>> production run, although I have already stated my objections about your
>>> workplan. If binding to the main ligand pocket is your ultimate goal, then
>>> you should steer the ligand to that direction. In contrast, if your goal is
>>> detection of allosteric pockets then I doubt that aMD is the right enhanced
>>> sampling method.
>>>
>>>
>>>
>>>> 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/
>>>
>>>
>>>
>>
>
>
> --
>
> ======================================================================
>
> 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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