Discussion Optimizing drug design

1. Summary of color-cards of first day DiscussionOptimizing drug design

2. Overzicht • Where are we now? • What does work? What does not work? • Where do we want to be? • What are the approaches?

3. Where are we now? • We have 'pretty' good models (one log unit accuracy) • Promising approaches for optimizing to those models; experimental validation is in its beginnings; as idea-generators they are used • Multiobjective Optimization strategies are available from other disciplines and can be used • Data Mining is 'pretty' advanced • Public Databases are still to be extended • Computer power is available but not fully exploited

4. What is desirable for the future?… and how can it be achieved? • The acceptance of the tools by the chemists should increase • A good communication language will help • A human centric decision process (the chemists wants to participate in the decision and discovery process) • Synthetic feasibility approaches • Tools should explain rationale • Good accuracy of the models is required • More Data, better descriptors could quantum based • Display model accuracy in decision process • A good understanding of what the objectives • What are models to predict human outcomes (2020 virtual human will help) • Objectives based on systems biology insights • More financial funding from industry and public research foundations

5. What is desirable for the future?… and how can it be achieved? • Exploration of a larger and more relevant part of chemical space • Concise definition of chemical space; maybe pharmacophore oriented; toxicophores and conformation? • Combine global and local searches'; uncertainty management (confidence bounds) • More constraint checks; use metamodels for rapid search • Dynamic knowledge use; closed loop learning • Use interactive learning …