tag:blogger.com,1999:blog-1136153439451224584.post8483948419512082975..comments2024-03-27T06:45:59.174-07:00Comments on Practical Fragments: Industrializing native MS: hundreds of fragments against dozens of targetsDr. Teddy Zhttp://www.blogger.com/profile/07288045760981372367noreply@blogger.comBlogger2125tag:blogger.com,1999:blog-1136153439451224584.post-28399868076121019922018-03-22T19:46:18.953-07:002018-03-22T19:46:18.953-07:00Hi Daniel,
You raise good points - promiscuity is...Hi Daniel,<br /><br />You raise good points - promiscuity is really a subjective concept, as evidenced by the fact that three clinical compounds against different kinases have all been derived from the same <a href="http://practicalfragments.blogspot.com/2015/10/fragments-in-clinic-plx3397.html" rel="nofollow">fragment</a>. I don't think there are hard and fast rules, and certainly if you have good structural information I wouldn't worry. The more difficult case is where you don't have a structure, such as in the case of <a href="http://practicalfragments.blogspot.com/2015/03/are-prats-privileged-or-pathological.html" rel="nofollow">PrATs</a> , which seem to show up as frequent hits but are difficult to move forward.Dan Erlansonhttps://www.blogger.com/profile/07927082337051189270noreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-12273794799303701332018-03-21T13:47:36.522-07:002018-03-21T13:47:36.522-07:00I'm curious about when we can say a fragment i...I'm curious about when we can say a fragment is promiscuous. Here they say 5 fragments bound to 5 proteins and 7 bound to 6 proteins. Then the authors say that binding to 6 proteins means they are promiscuous. I know it's relative to their screen, but are there more defined parameters that people have used in the past to declare a fragment as promiscuous? Perhaps low affinity combined with binding multiple proteins?<br /><br />Promiscuity at the start (assuming you don't have better options) doesn't necessarily mean med chem won't increase the specificity. Anonymoushttps://www.blogger.com/profile/12795947567929737181noreply@blogger.com