‘Library design‘ is a phrase that can encompasses many approaches and workflows including the design of screening libraries or the design of lead optimization libraries. We offer computational chemistry software and services that can help you with many of these design processes. Here we detail an approach that we have used successfully for the design of ‘focussed screening libraries’. That is libraries aimed at improving the hit rates of high or medium throughput screening for specific biological entities or families or at difficult targets such as protein-protein interactions.
Our approach to the design
Figure 1: Cresset’s approach to library design
The second stage is the most critical for the outcome of the project – idea generation. We find that our ideas materialize as we review and understand the previous work, including relevant ligands or crystal structures of the biological targets. As our analysis approaches its conclusion we begin generating and refining our ideas on new chemical entities that could form the heart of a new design. Of course every project is different but one common theme is that the first set of compounds are rarely the best and the ideas have to be refined and improved. As this progresses we take careful consideration of the potential to decorate cores with different R groups, the capabilities and thoughts of the synthetic chemists that will create the final compounds and the project brief. Bringing all these different components together is critical to success.
Why use Cresset?
Figure 2: Active compounds from focussed screening libraries designed by current Cresset staff
We have extensive library design experience using different approaches.1, 2 Our custom designs have been used throughout our industry from large pharmaceutical companies to small biotechs with diverse hits being obtained in kinases, GPCRs and ion channels.
Our range of software products inspire and inform our customers to generate the best molecules that they can and we use the same applications on our projects. However, our service offerings benefit from early access to new science features in the main software products (such as Activity Miner) and from access to unreleased software and cutting edge science. For example the ability to study the electrostatic environment of a protein active site and relate proteins using this description.