CDD’s recent live webinar event was a great success. To summarize, first, Dr. Chris Lipinski, reknowned medicinal chemist and CDD Scientific Advisory Board member, described the importance of considering enthalpy and entropy when optimizing for ligand affinity, and how this might differ between drug discovery techniques. Using the custom calculations available in CDD Visualization, we defined a new metric, the Simplistic Estimate of Enthalpy (SEEnthalpy), which opposes the number of hydrogen bond donors and acceptors against the number of rotatable bonds. We found that SEEnthalpy was on average higher for compounds developed through structure-based design (SBDD) compared to high throughput screening (HTS). Interestingly, exploring CDD’s public data, we also found that SEEnthalpy correlated with percent inhibition for more than half of the kinase assays we looked at. However, SEEnthalpy was not correlated with selectivity. Prof. Matt Soellner, a CDD customer, highlighted the metrics he uses within the CDD Vault to optimize for selectivity, and how he favors the cellular ligand efficiency metric compared to the typical biochemical ligand efficiency. Another calculation he finds particularly useful is the ratio of cellular to biochemical activity.
If you missed it, you can check out the complete presentation:
We greatly appreciate the smart and insightful questions from the audience. Due to time constraints, we apologize for not getting to address every question during the live event. Here is one final thought for a question posed during the webinar:
Why would water mediated ligand interactions lead to slow-offset? They are separate phenomena – thermodynamics and kinetics.“The depth of the energy well determines the free energy of the species (thermodynamics) The height of the energy barrier between species determines the rate of interconversion of species (kinetics)”
– Chris Lipinski, PhD
If you have further questions, comments, or ideas, please send us your thoughts at email@example.com.
This blog is authored by members of the CDD Vault community. CDD Vault is a hosted drug discovery informatics platform that securely manages both private and external biological and chemical data. It provides core functionality including chemical registration, structure activity relationship, chemical inventory, and electronic lab notebook capabilities!
CDD Vault: Drug Discovery Informatics your whole project team will embrace!