Drug Design

(1)

www.isb- sib.org

1.

^a

short film

produced with the help of graphic

designers Studio KO introduced the key notions for drug design (protein target, disease, ligand, docking,…)

Contact

info@atelier-drug- design.ch

Drug Design for high school students, high school teachers and the public at large

Our aim is to introduce, in an engaging and challenging way, concepts such as 3D structure, protein function, diseases and the role played by bioinformatics in drug discovery and development.

What do we propose ?

Blatter Marie-Claude^1,4, Daina Antoine², Baillie Gerritsen Vivienne¹, Marek Diana^3,4, Palagi Patricia M.⁴, Xenarios Ioannis^1,3, Schwede Torsten⁵, Michielin Olivier², Zoete Vincent²

1 Swiss-Prot group, Geneva, ²Molecular Modeling group, Lausanne, ³Vital-IT group, Lausanne, ⁴Training and Outreach group, ⁵ Computational Structural Biology group, Basel SIB Swiss Institute of Bioinformatics, Switzerland

Funded by the FNS (Agora) and ……

2.

‘manual docking’ of 3D-printed small molecules into a

3D-printed structure

representing the target protein ‘on scale’

and ‘manual docking’ with a camera system (

leap motion

)

3. tools embedded into a user friendly freely accessible web interface - www.atelier-drug-design.ch

allowing the design of new ‘virtual’ molecules, the visualization of their binding mode and the estimation of their affinity for the target protein

to be compared with ‘real’ existing drugs

5. pen and pencil activities

to illustrate how a computer encodes chemical structure (fingerprints) and how similarity between molecules is calculated.

The proposed workshops give

a simplistic yet realistic picture of using bioinformatics to support design of drug candidates

. Hands-on sessions are for cancer (target BRAF and IDO1) and pain (target COX) treatments. More than 200 people attended our pilot workshops. Many of them, even with very limited chemical background, became enthusiastic about the

challenge to sketch a molecule with possibly improved properties compared to well-known drugs

, in competition with other participants. According to the results of a first evaluation (n=35), the participants (over 16 years) really appreciate to

use bona fide bioinformatics tools

in such activities. The students interested in sciences for their future studies also appreciate to

discover a new professional field

. The workshop is proposed by the public labs ‘Chimiscope’ in Geneva and ‘l’Eprouvette’ in Lausanne. Current efforts of translation in English and German will broaden geographic area to all over Switzerland and abroad. Are you interested? Contact us!

a molecular docking simulation (AutoDock Vina)

predicts the binding mode and compares the affinity of

the molecule with the protein with existing drugs

(score)

4. direct link to expert tools to predict possible targets

(

SwissTargetPrediction) as well as important properties of the molecule to evaluate its potential to become a real drug (SwissADME)

draw a new molecule in 2D

(Marvin plot) 3D printed COX2

protein with 6 of its known ligands (non- steroidal anti-

inflammatory drugs)

iterative approach