tag:blogger.com,1999:blog-1136153439451224584.post3031812852230366565..comments2024-03-27T06:45:59.174-07:00Comments on Practical Fragments: Fragment specificityDr. Teddy Zhttp://www.blogger.com/profile/07288045760981372367noreply@blogger.comBlogger5125tag:blogger.com,1999:blog-1136153439451224584.post-90766684619198322622010-09-16T05:24:20.651-07:002010-09-16T05:24:20.651-07:00This comment has been removed by the author.Sarahhttps://www.blogger.com/profile/17085365364001204144noreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-15785028347773766772010-09-08T22:10:43.385-07:002010-09-08T22:10:43.385-07:00Okay, ran 2YXJ (Bcl-xL with the ABT compound), 1R2...Okay, ran 2YXJ (Bcl-xL with the ABT compound), 1R2D, and 1MAZ (two apo structures) in FTMap.<br /><br />Now there's a considerable conformational change on binding of ABT in the residues from 100 to 129. But the results were still pretty good.<br /><br />Now in 2YXJ the top ranked hot spot is where the benzylthioether is and it extends to the nitro group. In both 1R2D and 1MAZ this spot is blocked by residues Arg100 and Tyr195 but in 1MAZ there is still a cluster composed of just acetone, formamide, and formamine (ranked 7th).<br />Still in 2YXJ the 2nd, 3rd, and 5th cluster covers the chlorine and the two rings attached to it. In 1R2D and 1MAZ Phe105 covers the chlorine and the first ring but in 2YXJ Phe105 switches into an area ranked 5th (and partially 1st) in 1MAZ and 4th in 1R2D.<br />Moving down to the 6th ranked site, it is placed in the same spot as the two 6-membered rings of which one has two nitrogens. This is the top ranked site in 1R2D and 2nd in 1MAZ.<br />Bizarrely the 3rd ranked site in 1MAZ/1R2D is not detected in 2XYJ at all. The only difference is that His177 and Asn128 move slightly away and Tyr173 moves slightly closer in the inhibitor bound conformation.<br /><br />So basically the inhibitor covers ~3 hot spots by binding to them and 2 allosterically. And it remodels all but one of the hot spots it binds to.<br /><br />Now unfortunately I'm between jobs so I don't access to the article and can't tell if it's the same spot =(<br /><br />I can send you the files if you want to have a look.<br /><br />Morten GMorten Grøftehaugehttps://www.blogger.com/profile/05252471246488393284noreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-44906429744201143102010-08-19T08:40:15.369-07:002010-08-19T08:40:15.369-07:00Good question. Unfortunately FT-Map is only availa...Good question. Unfortunately FT-Map is only available to academics, but please post if you find the answer.Dan Erlansonhttps://www.blogger.com/profile/07927082337051189270noreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-84928854531404713132010-08-19T01:05:06.635-07:002010-08-19T01:05:06.635-07:00I should probably do this myself and probably also...I should probably do this myself and probably also will at some point but... those anyone know if the hot spots they find are the same ones found by http://ftmap.bu.edu/ < presumably a hot spot finding web service?Morten Gnoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-26502664203629655062010-08-09T07:46:52.193-07:002010-08-09T07:46:52.193-07:00I'm curious whether many of the nonspecific hi...I'm curious whether many of the nonspecific hits might go away if assayed in the presence of detergent.Donnie Berkholzhttps://www.blogger.com/profile/12600163525296733040noreply@blogger.com