tag:blogger.com,1999:blog-1136153439451224584.post2403563782541459833..comments2024-03-27T06:45:59.174-07:00Comments on Practical Fragments: Biofragments: extracting signal from noise, and the limits of three-dimensionalityDr. Teddy Zhttp://www.blogger.com/profile/07288045760981372367noreply@blogger.comBlogger3125tag:blogger.com,1999:blog-1136153439451224584.post-19157674224005227792014-05-13T06:08:14.876-07:002014-05-13T06:08:14.876-07:00 A recent paper in JACS concludes that fragment ba... A recent paper in JACS concludes that fragment based approaches to substrate discovery are unlikely to be successful.<br /><br />http://pubs.acs.org/doi/abs/10.1021/ja501354qNatenoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-36928919507788413602014-05-08T14:52:51.702-07:002014-05-08T14:52:51.702-07:00Although not strictly fragment-based, a colleague ...Although not strictly fragment-based, a colleague in our lab has had success with a related approach. She relied on molecular docking of the entire KEGG library of metabolites and the genome context of the unknown bacterial enzymes to assign function. <br /><br />http://www.ncbi.nlm.nih.gov/pubmed/24056934<br /><br />To me, this seems like a kind of in-silico parallel to the experimental approach discussed above. The experimental approach of looking for fragment binders is perhaps handicapped by the small size and diversity of the collection. Docking used in this kind of exploratory analysis is not limited by library size or complexity.Michael Chimentihttp://michaelchimenti.comnoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-6598942474209640352014-05-05T15:32:22.662-07:002014-05-05T15:32:22.662-07:00I saw this paper and was intrigued. It is a very ...I saw this paper and was intrigued. It is a very similar approach to the Emerald Fragments of Life. This is also something I have done in that past. It is my experience /impression that this is not a fantastic source of fragment hits. I think you would be just as successful starting with a library of all 20 amino acids as with "substrate fragments". Their approach might be useful for a target validation or "What the heck does this enzyme do study", but I am wholly unconvinced that this is a good entree into any sort of fragment diversity. Dr. Teddy Zhttps://www.blogger.com/profile/07288045760981372367noreply@blogger.com