Today’s post, contributed by InnoCentive Founder Alph Bingham, addresses the gaps in most molecular compound libraries, and the new ways InnoCentive is reaching out to Solvers to help close those gaps.
The very concept of molecular space is an intriguing one. But even after decades, it seems a rigorous (rigid?) standard has never developed for defining this space. Are the axes topological alone? Are they graph theoretical and limited to connectivity? Are they electronic? Do they include physical or chemical properties associated more with the nature of the substance than the behavior of a single molecule? Well, yes. All of the above, depending on application, assumptions and objectives.
But even without a rigorous set of definitions, the metaphor alone allows us to think carefully about the design of our experiments, the creation of our libraries (collections of molecules), the subsets we’ll screen and the way we’ll respond to hits and build out SARs (structure activity relationships). In a perfect world, our libraries are “smooth” not “lumpy.” They fill out molecular space evenly, not like swiss cheese with big holes. And the density is a factor under OUR control. We use low density compound collections when we must screen across vast territories and we use high density collections when prior screens and experiences have told us the regions of space wherein lie interesting possibilities. Read more