Day 1: Rapid 3D-QSAR and Lead Optimization with the
Topomer Technology

Despite the constantly growing number of resolved protein structures there are still many targets not accessible for structure-based design such as docking. Nevertheless there is information on ligands and their activity. This knowledge can guide the search for similar but new active compounds on the one hand side and can be used for QSAR-studies on the other side.

So during the first day of the workshop we will do virtual screening with Topomer Search which is a fast shape based searching approach.

Here we will

• Perform lead-hopping
• Find new R-groups that maintain shape and pharmacophore features.
• Find new scaffolds that maintain molecular shape.

As the Topomer concept enables rapid and consistent alignments of compounds it will be applied to generate a 3D-QSAR model. With such an established Topomer CoMFA model R-groups can be searched and immediately predicted in their activity.

• Generate ideas for lead optimization that are likely to increase activity.

Day 2: De-novo Design

Finally the course will cover the technique of De-Novo Design with the help of the Evolutionary Algorithm Inventor (EAI). We will use in the MUSE implementation. Starting from “scratch” MUSE will invent completely new compounds during several iterations. Each invented structure will be compared and scored against known structures. Resulting compound lists will be further filtered and ranked based on diverse criteria.

The course will further demonstrate that the users can provide their own scoring function which then will guide the invention process.