An efficient visualization tool for the analysis of protein mutation matrices

1. An efficient visualization tool for the analysis of protein mutation matrices Maria Pamela C. David, Carlo M. Lapid and Vincent Ricardo M. Daria Computational Science Research Center University of the Philippines, Diliman

2. Outline • Visualization • A crash course on protein structure, function and engineering • Protein mutation matrices • Generation • Data • Visualization • Applications of visualization

3. Visualization

4. Visualization

5. Visualization

6. Visualization • “Our species relies on vision over all other senses” (about half of the human brain is devoted directly or indirectly to vision) • “We learn about 11% audibly and 83% visually” • ~50% of our brain gets involved in visual processing • Other perceptual channels can be used : - They work in parallel as long as they don’t conflict - In a conflict, the visual channel will dominate

7. Crash course on protein structure and engineering

8. Protein mutations?

9. Protein mutation/substitution matrices • Analysis of evolving sequences/sequences with high variability • Would have applications in artificial protein design

10. W S T D R A K I Y E G L E R G D T G K G Matrix generation

11. Hydrophilicity Size and Polarizability Charge and polarity D → G R → E T → I S → L S → K W → R T → D Matrix generation W S T D R A K I Y E G L E R G D T G K G Physico-chemical properties • Note: • Alignment should be good • Primer-derived sequences should be removed

12. Sample mutation matrix Replacement residues, increasing hydrophilicity Replaced residues, increasing hydrophilicity

13. Image equivalent Lower hydrophilicity Higher hydrophilicity

14. Tool 1: Matrix scaling W L F I M V Y P A T C Q G K S H N E R D

15. Tool 2: Matrix comparison Find mutations exclusive to either matrix W L F I M V Y P A T C Q G K S H N E R D W L F I M V Y P A T C Q G K S H N E R D Matrix 1 Matrix 2

16. Tool 2: Matrix comparison W L F I M V Y P A T C Q G K S H N E R D Matrix 2 only Matrix 1 only

17. Complementarity Determining Region FRamework Application 1: antibody engineering

18. Application 1: antibody engineering W L F I M V Y P A T C Q G K S H N E R D W L F I M V Y P A T C Q G K S H N E R D FR mutations CDR mutations

19. D T I D K R Application 1: antibody engineering W S T D R A K I Y E G L E R G D T G K G Engineered antibody

20. Application 2: vaccine design

21. Application 2: vaccine design Lower hydrophilicity Higher hydrophilicity

22. Application 3: biosensor design

23. Smaller residues Larger residues Application 3: biosensor design

24. Other advantages of visualization

25. Conclusion • Visualization plays a key role in analysis • Quicker elucidation of patterns • Find those that were not immediately obvious • Key applications of protein mutation matrix visualization • Evolution studies • Protein engineering • Image manipulation and analysis techniques may be applied to images

26. Current activities + future targets • Matrix generation tool development • Prototype hosted at the CSRC site • Migrate from Matlab to open source software (i.e. Scilab/Octave + PERL/Tcl/Tk) • Offer full matrix generation + visualization package online