[Dock-fans] 回复: some quetion of DOCK Anchor-and-Grow.

Sudipto Mukherjee sudmukh at yahoo.com
Wed Mar 27 09:01:42 PDT 2013


Hi LiLei,

As Trent suggested, using the verbose flag will help you get a better idea of where in the anchor-and-grow process the particular ligand fails. 

It sounds like you are successfully docking in some of your ligands, just not all of them. Visualize the top scored poses for the small molecules that complete growth to check if you are getting reasonable docked poses (e.g. Viewdock tool in Chimera). 

Since the native ligand fails to complete growth, there might be issues with your setup. Visualize the native ligand mol2 file bound to the receptor mol2 file you are using for preparing the grid and check for potential clashes. Minimize the native ligand on the receptor coordinates (use continuous score instead of grid score, no orienting or flexible ligand, just minimization). How many rotatable bonds are there in the native ligand? 
 
Regards
Sudipto Mukherjee, PhD
Dept. of Chemistry, Temple University
1901 N 13th St, Philadelphia, PA 19122

P.S. Please send your replies to the dock-fans mailing list so that everyone in the community can participate in the discussion. 


________________________________
 From: LiLei <284246396 at qq.com>
To: Sudipto Mukherjee <sudmukh at yahoo.com> 
Sent: Wednesday, March 27, 2013 11:46 AM
Subject: 回复: [Dock-fans] some quetion of DOCK Anchor-and-Grow.
 

Hi Sudipto Mukherjee,

Thanks for your help and i'm sorry about trouble you again.I have docked the native ligand with target protein, unfortunately, the same error was appeared. By the way, I have checked one of the ligand which could not complete growth,the number of rotatable bonds was 4 and the molecular weight was 309.283,so it was small ligand.  So maybe  something wrong when i create the spheres.

There are a question about create sphere,i  got some information from DOCK6.5 User Manual,the dms default density setting of 1.0 gives ~5.0dots/A2 whereas the Chimera default is 2.0 dots/A2,so when we create sphere and surface of a small pocket,should we use the small radius(like dms 1.0A) rather than big radius(chimera default 2.0A)?

Thankyou very much.
Regards

LiLei



------------------ 原始邮件 ------------------
发件人: "Sudipto Mukherjee"<sudmukh at yahoo.com>;
发送时间: 2013年3月27日(星期三) 晚上9:24
收件人: "李雷"<284246396 at qq.com>; "dock-fans"<dock-fans at docking.org>; 
主题: Re: [Dock-fans] some quetion of DOCK Anchor-and-Grow.

Hi 李雷,

The error you received indicates that no reasonable pose could be found during sampling. While DOCK suggests two possible reasons why this could happen, there might be other causes as well. 

Before attempting an actual virtual screen, it is a good idea to check your docking setup to make sure there are no obvious problems. First check the placement of the spheres used to orient the anchor. Are the spheres located within the target active site? Does the native ligand dock back in successfully? This error can occur when the ligand being docked in is simply too big to fit inside the active site. How many rotatable bonds are present in the ligand you are attempting to dock in. DOCK is designed primarily with screening small molecules in mind. 
 
Regards
Sudipto Mukherjee, PhD
Dept. of Chemistry, Temple University
1901 N 13th St, Philadelphia, PA 19122


________________________________
 From: 李雷 <284246396 at qq.com>
To: dock-fans <dock-fans at docking.org> 
Sent: Wednesday, March 27, 2013 4:42 AM
Subject: [Dock-fans] some quetion of DOCK Anchor-and-Grow.
 

Hi everyone,
     I have used DOCK6.5 to do some work about virtual screen. when I execute DOCK of a target protein and a random ligand use Anchor-and-Grow method, there are some information feedback as follows:
 ERROR:  Could not complete growth.
         Confirm that the grid box is large enough to contain the ligand,
         and try increasing max_orientations.

so I try to increase the size of BOX,from 6.0A to 8.0 10.0 12.0 but it still  report errors;I also increase the default max_orientations 500 to 1500 2000 even 10000 but the error was still exist.
could anyone  tell me the reason and how to deal with this question. Thankyou very much !
Regard,

LL_thuder
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