Re: [External] Boost value in aMD simulation

From: James Starlight (jmsstarlight_at_gmail.com)
Date: Tue Aug 19 2014 - 13:45:58 CDT

Thanks for suggestions!

Regarding simulation with the ligand: does the idea to perform clustering
of the receptor's regions (loop) being interacting with different ligands
seems good (e.g to compare results of apo-holo simulation to detect some
shared clusters between bpoth systems)?

Regarding cut-off: when I reduced it to 1-2 A I still obtain 6-7 clusters
but most of the conformers were as the outliers (not in any of these
clusters).

Regarding dendrograms: for me better to find some python package for such
task :-) I'll try to check for it! Might the g_cluster be also usefull
within my taks besides of obtaining representative structures from each
clusters?

James

2014-08-19 14:24 GMT+04:00 Thomas Evangelidis <tevang3_at_gmail.com>:

>
>
> On 19 August 2014 12:56, James Starlight <jmsstarlight_at_gmail.com> wrote:
>
>> Thomas,
>>
>> I've noticed that in case of *long* loops the big uncertainly exist
>> during its clustering using only rmsd criterium: for instance with the big
>> cutoff (e.g 3.5-4 A)all
>>
>
> This is a big cutoff.
>
>
>
>> conformations could be grouped in the few (up to 10) clusters with small
>> numbers of structures not in one of the clusters (outliers?) but in this
>> case representative structure from every cluster are not very differs from
>> each others in conformations (because most of its part has not any 3D
>> structure). BTW do you know any software
>>
>
> Do you mean secondary structure here?
>
>
>> which could produce distribution patterns on the diagram grouping all
>> clustered together (I'm using vmd cluster plugin where I could not find
>> such representations)?
>>
>>
> Like a dendrogram? I usually do this in R but using it's internal
> clustering algorithms.
>
>
> However, my impression is that you spend too much time in the
> preliminaries of the project. The essence is the simulation with the
> ligands. So just pick up one starting conformation and move forward. You
> may spend many weeks trying different clustering schemes and still not find
> a solution that satisfies you.
>
>
>
> 2014-08-18 11:21 GMT+02:00 Thomas Evangelidis <tevang3_at_gmail.com>:
>
> The right way is to reweight the clusters, but as I stated before
>> reweighting aMD is not accurate for such big systems. If the number of
>> frames is not too big and you can do clustering, just go for that solution
>> which is simpler.
>>
>>
>>
>> On 18 August 2014 11:25, James Starlight <jmsstarlight_at_gmail.com> wrote:
>>
>>> 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/
>>>>
>>>>
>>>>
>>>
>>
>>
>> --
>>
>> ======================================================================
>>
>> 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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