2010/12/12 Deepangi Pandit deepangi.pandit++
http://gmail.com" target="_blank">gmail.com
<owner-chemistry _ ccl.net>
Sent to CCL by: Deepangi Pandit [deepangi.pandit|,|gmail.com]
Thank you Peter, for your detailed reply. I would just like to clarify
my case based on your questions.
> 1 : Do you want to apply this method on a database of proteins or just a
few structures?
I am looking at just a few structures to identify the putative drug
binding site. I have PDB files of protein structures (of course,
without the compound) and have experimental data which suggests the
compound is binding but do not know where.
> 2 : Do you want to identify putative drug binding sites or whatever binding
site a method could find (general purpose pocket prediction)
I am trying to identify the putative drug binding sites not general
purpose pocket prediction
> 3 : Do you want to find conserved pockets among homologs?
This is not my primary goal.
Best,
Deepa
On Sat, Dec 11, 2010 at 4:45 PM, Peter Schmidtke
pschmidtke[-]mmb.pcb.ub.es <owner-chemistry|-|ccl.net> wrote:
>
> Sent to CCL by: Peter Schmidtke [pschmidtke[*]mmb.pcb.ub.es]
> Dear Deepangi,
>
> protein-ligand binding site detection is a very active field and there
> is a large variety of methods out there.
> Since the publication of PocketPicker
> (http://www.journal.chemistrycentral.com/content/1/1/7/abstract/)
lots
> of newer methods used the comparative table that was published with
> PocketPicker (table 2). A very recent example is the paper by Andrea
> Volkamer, where you have an update of this table with a few more recent
> methods (http://pubs.acs.org/doi/full/10.1021/ci100241y).
>
> This comparison is definitely arguable, but at least it gives some hint
> on general pocket prediction performance. In order to find the perfect
> method for your purpose you should maybe clarify what is the
> functionality your are seeking. There are lots of webservers out there,
> methods you have to pay and also free methods.
>
> Some questions that could influence your choice :
>
> 1 : Do you want to apply this method on a database of proteins or just
a
> few structures?
> 2 : Do you want to identify putative drug binding sites or whatever
> binding site a method could find (general purpose pocket prediction)
> 3 : Do you want to find conserved pockets among homologs?
>
> Concerning question 1, if you just need a method for a few structures
> you can go for slower programs (mostly energy based algorithms) like
> SiteMap from Schrödinger (but you need a license) Q-SiteFinder or
> PocketPicker or Vice (I think it's sold by Tripos) There are surely
more
> than that.
> If you need to process a large number of structures, considering
> geometry based methods might become an interesting choice. Choices
could
> be Ligsite, fpocket, PASS, SiteFinder (included in MOE by CCG) ...
>
> Regarding question 2. Pocket prediction is not equal drug binding site
> prediction. Recent druggability prediction methods have been published
> and some scores are available ready for use in SiteMap (I don't know
if
> you still have to calculate it or if they finally included it into the
> SiteMap distribution) and fpocket. I suspect also QSiteFinder might
give
> indications on druggability (I extrapolate from the methodology I just
> read very quickly, so maybe I'm wrong here ;) ).
>
> Regarding question 3, I think ligsite csc can help there
> (http://projects.biotec.tu-dresden.de/pocket/), or else
hpocket, which
> is part of the fpocket webserver :
> http://bioserv.rpbs.univ-paris-diderot.fr/fpocket/
>
> I hope that this gives you at least a direction, there are really lots
> of methods and it is indeed not easy to know which one to use ;)
>
> Ah, I nearly forgot, metapocket2.0 is a sort of consensus pocket
> prediction method that makes use of LIGSITEcsc, PASS, Q-SiteFinder,
> SURFNET, Fpocket, GHECOM and ConCavity. This has again advantages and
> disadvantages, but well, at least you know that it exists ;)
>
> Good luck.
>
> Peter Schmidtke
>
>
>
>
> On 12/11/2010 06:44 PM, Deepangi Pandit deepangi.pandit~!~gmail.com wrote:
>> Sent to CCL by: Deepangi Pandit [deepangi.pandit(!)gmail.com]
>> Dear All:
>> I tried to search literature and Internet to find a reliable method
>> that I can use to identify protein-ligand binding site. I came
across
>> number of papers but I am unable to evaluate the methods before I
>> start using them. I was also unable to find a review which compares
>> the methods. It seems method can be broadly classified as
"Geometry
>> based" and "Energy Based". Could you please recommend
from your own
>> experience which method gives reasonable results. Also, feel free
to
>> share pros and cons of the method.
>>
>> Thank you.
>> Deepa
>>
>> List of methods I came across
>>
>> Q-Site Finder
>> http://www.bioinformatics.leeds.ac.uk/qsitefinder
>>
>> Surface triplet propensities
>> http://opus.bch.ed.ac.uk/stp
>>
>> Screen
>> http://interface.bioc.columbia.edu/screen>
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