Thursday, June 16, 2011

the road to mcule

As a first post in the mcule blog we thought it was a good idea to explain our motivations and how the original idea of mcule came. It all started with the observation of an unmet need. Well, it was actually an unmet need of the storyteller :)

I started my PhD in 2004. As a subject my supervisor suggested me the histamine H4 receptor – a novel and very interesting drug target. Only a few selective H4 ligands were known at that time, so any new ligands would have been of great value. We had good experiences with histamine receptor homology models in the past, so we decided to build a structural model for the H4 receptor, and screen compounds virtually in the hope of finding new H4 ligands. After selecting one suitable model for screening, we were facing the first major problem: how could we screen all commercially available compounds? While the ZINC database offered screening libraries of a few vendor companies it only represented a small portion of the purchasable chemical space and most of the libraries were out-of-date. Still, ZINC was a great help and served as a starting point for our screening database. We updated some libraries directly form the vendors and also added some new libraries not included in ZINC. This took, however, a long time (seeking vendors, registering on their website, waiting for passwords, downloading libraries or waiting for their CD to arrive, etc.). Preparation of the newly added compounds (prediction of protonation states, 3D coordinate generation, ID generation, etc.) also took a while but after a few more weeks the database was ready for screening.