tag:blogger.com,1999:blog-1136153439451224584.post6027684141447683432..comments2024-03-27T06:45:59.174-07:00Comments on Practical Fragments: Are enthalpic binders more selective than entropic binders?Dr. Teddy Zhttp://www.blogger.com/profile/07288045760981372367noreply@blogger.comBlogger2125tag:blogger.com,1999:blog-1136153439451224584.post-60232396438728093392011-12-08T21:21:46.684-08:002011-12-08T21:21:46.684-08:00My challenge to those who advocate the benefits of...My challenge to those who advocate the benefits of enthalpy-driven binding is: Please tell me how an isothermal physiological system 'senses' that the binding is enthalpy-driven. The contribution of an individual protein- ligand contact is not strictly an experimental observable and there. I've never seen any convincing data analysis that supports the links between enthalpy and polar interactions and between entropy and non-polar interactions. There are situations (e.g scale up of synthesis) where changes in enthalpy (and volume) are highly relevant. <br /><br />I agree that excessive lipophilicity is a bad thing (although the trends are not always as strong as 'creative' ways of plotting the data might suggest). However, I'm not sure what calorimetry is adding to logP/D in terms of quantifying risk.Peter Kennyhttps://www.blogger.com/profile/12180360326821860667noreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-68245528352840790292011-12-08T06:17:08.047-08:002011-12-08T06:17:08.047-08:00So, my cynical self always ask, "If I give th...So, my cynical self always ask, "If I give this data to a medicinal chemist (enthalpic vs. entropic), how will he use it to decide which compounds to make?" To often, in my experience, we think we are being so clever with new metrics, new approaches, new parsing of data, but in the end what matters most is did the data get used in the decision to make new compounds? I would be curious to hear from molecule makers how they would use this knowledge in their decision making process.Dr. Teddy Zhttps://www.blogger.com/profile/07288045760981372367noreply@blogger.com