Molecular modelling can help reduce the time and risks of drug development. It is applied to target structural characterization, developing focused libraries for hit discovery, and lead development and optimization. Fragment-based drug design is an important advance, where drug candidates are built inside the target's binding site using small molecule fragments to improve affinity from micromolar to millimolar to nanomolar levels. Molecular modelling supports medicinal chemistry decisions by providing structural insights into how drug candidates interact with their targets.

1. Computational Structure-based Drug Design Fragment-based drug design Hit and Leads by structural design Molecular Modelling Mini Tutorial

2. Discovery of a new drug is a long and costly process Time 20 - 40 Months Value 2.5 – 7 Millions Source: Bogdan, B and Villiger, R. Valuation in Life Sciences, 2007, Springer Molecular Modelling Mini Tutorial Target Validation Lead optimization Hit discovery

3. The risk of failure is very high Drug development success rates Reasons of abandonment Source: Bogdan, B and Villiger, R. Valuation in Life Sciences, 2007, Springer Molecular Modelling Mini Tutorial 15.8% Oncology 28.1% Infections 15.4% Immunology 17.5% Cardio vascular 14.5% Central nervous system Rate Disease Group 9.0% Other 19.6% Safety 33.8% Economics 37.6% Efficacy Rate Reason

4. Molecular Modelling can help to reduce the drug development time and risk of failure Computational chemical and structural biology applied to: Molecular Modelling Mini Tutorial Target structural characterization Development of focused libraries for hit discovery Lead development and optimization Target:drug structural characterization

5. Innovative drug development platforms Fragment-based drug design approach One of the most important advance in drug discovery Drug candidates are built inside the target binding site using small molecule fragments Lead fragment Fragment grow Drug candidate Micromolar affinity Millimolar affinity nanomolar affinity Molecular Modelling Mini Tutorial Target structure Target structure Target structure

6. Detailed target:drug candidate structural characterization Molecular Modelling Mini Tutorial Support you Medicinal Chemistry decisions with our structural and modelling information Get a structural picture of how your drug candidates interact with your target

7. Molecular Modelling can support your research & development effort on: Target structural characterization Focused libraries for Hit and Lead discovery Lead potency and selectivity optimization Natural product redesign Structure characterization Molecular Modelling Mini Tutorial Dr. Nuno Micaelo Researcher, Aveiro University [email_address]