1. MSDmotif 1 Adel Golovin Protein Site and Motif search Biosapiense network of excellence

2. MSDmotif 2 Overview crystallographerbiochemistry Ph.d students Pharma researchScientist Oracle Service Database tomcat J2EE application

3. MSDmotif 3 Search options

4. MSDmotif 4 Search example 1nio + Where N covalently binds sugar: Super-secondary structure Strand – <= 5 residues loop – Strand + N Glycosylation pattern N{P}[ST]{P} + 2-3 residues gap 150.000 coordinate entries

5. MSDmotif 5 Search results

6. MSDmotif 6 Binding statistics Molecule binding Pair binding Motif binding 3D Environment ? Chemical fragments Main/Side chain Plane interactions Stats on a family RR calculation

7. MSDmotif 7 Data retrieval Chemical search PDB/CIF files with ligands and those 4.2 Å environment Web Service XML request eFamily XML Statistics in text files Sequence alignment files Distributed Annotation System (DAS) HTTP URL request DAS XML HTTP request text files, XML, PDB,CIF,ALN…

8. MSDmotif 8 Approach Where to start? Results presentation? See: help->examples

9. MSDmotif 9 Ligand approach Staurosporine Kinase inhibitor Ligand fragment binding statistics

10. MSDmotif 10 Molecule binding interface

11. MSDmotif 11 Protein sequence approach Tyrosine protein kinases specific active-site signature: [LIVMFYC]-{A}- [HY]-x-D- [LIVMFY]- [RSTAC]-{D}- {PF}-N- [LIVMFYC](3) Motif binding statistcs Ligand fragments

12. MSDmotif 12 Motif binding statistics

13. MSDmotif 13 Protein sequence approach 2 Tyrosine protein kinases specific active-site signature: [LIVMFYC]-{A}- [HY]-x-D- [LIVMFY]- [RSTAC]-{D}- {PF}-N- [LIVMFYC](3) Search3D alignment

14. MSDmotif 14 Protein structure approach 3D fragment SearchSequence pattern φ/ψ sequence -156/-155,-103/17,-134/161

15. MSDmotif 15 Protein structure approach 2 Sample motif from a PDB entry Complete graph search by CA or end of side chain positions 3D alignment of the hits S CA

16. MSDmotif 16 Computer Aided Drug Design CADD vHTS Sequence analysis Homology modelling Similarity search Drug Lead optimisation Physicochemical modelling Drug Bioavailability bioactivity

17. MSDmotif 17 Computer Aided Drug Design Modelling Prediction Analysis Search Alignment A good prototype is often better than a best model Sequence and 3D multiple alignment largely improve model quality

18. MSDmotif 18 Availability www.ebi.ac.uk/msd-srv/msdmotif/ MSD: www.ebi.ac.uk/msd GNU public licensegolovin@ebi.ac.uk