[Dock-fans] Re: Dock-fans Digest, Vol 17, Issue 10 (orientation number)

Demetri Moustakas moustakas at gmail.com
Tue Nov 15 18:56:44 PST 2005


Dear Le,

I may have oversimplified in my previous message to you- both the 
orientational and conformational sampling are important.  An easy test 
that you can use to determine if you are sufficiently sampling in your 
system is to run the same docking calculation several times using 
identical parameters except for the random number generator seed value. 
  If you change this value, and find that the poses/scores generated by 
DOCK are very similar (have a low variance), then you are sampling 
sufficiently.

If there is a large variance in the scores you obtain, you should 
consider increasing the number of orientations, and/or the number of 
conformations (Nc).  It is also possible that you may need to increase 
the number of spheres you are including in the binding site of your 
receptor.

Our preliminary characterization finds that for flexible ligand docking, 
you should probably use the following parameter values:

max_orientations			500-1000
number_confs_per_cycle			50
simplex_anchor_min_max_iterations	100
simplex_flex_min_max_iterations		25
simplex_final_min_max_iterations	100

These seem to optimize DOCK's structure prediction success rate while 
minimizing the required computation time.

Cheers,
Demetri


Le Tien Dung wrote:
> Dear Dr. Demetri
>  
> Thank you for the useful information regarding the orientation (which I 
> mistakenly named as conformation).
>  
> Could you and other Dock-men explain me about the number of orientation 
> that we should try? This is important for me because I do not have a 
> powerful computer to make it sample a number well upon the required values.
>  
> Does this value depend upon the nature of of the molecules? (such as the 
> number of heavy atoms). Though I used to set as the default value (500), 
> the dock out file usually gives the values that dock has sampled around 
> 200-300 (in my case).
> Does that value means that 500 orientation sampling is sufficient?
>  
> Thank you for your kind reply
>  
> Best regards
>  
> Le
> 
> */Demetri Moustakas <moustakas at gmail.com>/* wrote:
> 
>     Dear Dr. Zhu,
> 
>     The reason this sometimes occurs is that DOCK relies upon a random
>     number during its use of the simplex minimizer. In the situation you
>     described, the random numbers generated while docking the molecule in
>     the database will differ from the random nubmers generated while
>     docking
>     the molecule alone.
> 
>     DOCK will generate a set of ligand orientations of the ligand in the
>     receptor, which will be identical in your two cases since this step
>     does
>     not rely on the RNG. However, once DOCK energy minimizes each of these
>     initial orientations, the differences will appear, since the minimzer
>     relies on the random numbers. It can be possible that in one case,
>     DOCK finds a lower energy minimized ligand pose that the other case
>     misses because of the different random numbers.
> 
>     This is an indication that you are not sufficiently sampling
>     orientations of your molecules. If you sample more orientations, you
>     will find that these discrepencies go away, since you increase the
>     probability of finding the lowest energy poses by starting from more
>     initial orientations.
> 
>     Best,
>     Demetri Moustakas
> 
>      >
>      > ------------------------------
>      >
>      > Message: 3
>      > Date: Sat, 12 Nov 2005 09:51:15 +0800
>      > From: "=?gb2312?B?1uzP/sDa?="
>      > Subject: [Dock-fans] dock5.3 question!
>      > To: "dock-fans"
>      > Message-ID: <200511120151.jAC1pQd00633 at blur.compbio.ucsf.edu>
>      > Content-Type: text/plain; charset="gb2312"
>      >
>      > Dear sir,
>      > I docked a database today using dock5.3. However, I find energy
>     Score is not uniform with IC50.So I extract one molecular from the
>     database and then docking in the same condition.The result is the
>     energy Score is different from the energy Score in database. Why?
>      > Best wishes
>      >
>      > ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡
>      >
>      >
>      > ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡xiaolei zhu
>      > ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡zxl102623 at 126.com
>      > ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡2005-11-12
>      >
>      >
>      > ------------------------------
>      >
>      > Message: 4
>      > Date: Sat, 12 Nov 2005 00:40:52 -0800 (PST)
>      > From: Le Tien Dung
>      > Subject: Re: [Dock-fans] dock5.3 question!
>      > To: "ÖEþÀÚ" , dock-fans at docking.org
>      > Message-ID: <20051112084052.79939.qmail at web51407.mail.yahoo.com>
>      > Content-Type: text/plain; charset="iso-8859-1"
>      >
>      > hi there,
>      >
>      > I also observed the same phenomenon, however, I think a small
>     difference in scores for different runs is just fine. You should
>     also check if the number of conformations sampling is similar in
>     both batch run and single molecule run. I guess this may also affect
>     the score.
>      >
>      > Regarding the IC50 thing, in my opinion, we should not rely much
>     on IC50 but the Ki. This is especially the case when the inhibition
>     is non-complete (partial inhibition). When the inhibition is strong
>     (at very low molar concentration of inhibitors) but it could only
>     inhibit 49% of the total activity when saturated, then we cant find
>     the IC50 value, but we do get the Ki.
>      >
>      > Please correct me if I am wrong
>      >
>      > Thanks
>      >
>      > Le
>      >
>      > ցEþÀÚ wrote:
>      > Dear sir,
>      > I docked a database today using dock5.3. However, I find energy
>     Score is not uniform with IC50.So I extract one molecular from the
>     database and then docking in the same condition.The result is the
>     energy Score is different from the energy Score in database. Why?
>      > Best wishes
>      >
>      > ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡
>      >
>      >
>      > ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡xiaolei zhu
>      > ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡zxl102623 at 126.com
>      > ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡2005-11-12
>      > _______________________________________________
>      > Dock-fans mailing list
>      > Dock-fans at docking.org
>      > http://blur.compbio.ucsf.edu/mailman/listinfo/dock-fans
>      >
>      >
>      >
>      >
>      >
>      > Le Tien Dung, PhD
>      >
>      > The Microbial Function Laboratory
>      > National Food Research Institute (NFRI)
>      > Kannondai 2-1-12, Tsukuba, Ibaraki 305-8642 - JAPAN
>      >
>      > E-mail: ledt at affrc.go.jp
>      > URLs: http://www.nfri.affrc.go.jp & http://www.cynosura.org
>     (personal)
>      >
>     _______________________________________________
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> 
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