An efficient visualization tool for the analysis of protein mutation matricesMaria Pamela C. David, Carlo M. Lapid and Vincent

Ricardo M. Daria

Computational Science Research CenterUniversity of the Philippines, Diliman

Outline

Visualization A crash course on protein structure, function

and engineering Protein mutation matrices

Generation Data Visualization

Applications of visualization

Visualization

Visualization

Visualization

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

Crash course on protein structure and engineering

Protein mutations?

Analysis of evolving sequences/sequences with high variability

Would have applications in artificial protein design

Protein mutation/substitution matrices

Matrix generation

A D R TS W

G

G

G

E

G

E

K

K

L

T

I

D

Y

R

Matrix generation

Note:

1. Alignment should be good2. Primer-derived sequences should be removed

A D R TS W

G

G

G

E

G

E

K

K

L

T

I

D

Y

R

Size and Polarizability

D → G

S → K

Charge and polarity

R → E

W → R

T → D

Hydrophilicity

T → I

S → L

Physico-chemical properties

Sample mutation matrix

  W L F I M V Y P A T C Q G K S H N E R D

W 0 0 0 0 1 37 3 0 36 0 2 1 4 0 0 35 25 0 0 0

L 2 0 59 225 155 76 0 26 73 36 37 110 40 4 149 2 4 110 7 76

F 36 6 0 1 0 3 3 0 46 0 0 0 79 2 4 38 37 39 0 3

I 41 92 7 0 148 235 35 0 0 143 0 0 39 49 24 1 74 0 73 2

M 36 32 72 15 0 50 0 0 3 3 0 37 26 10 5 0 2 1 64 4

V 1 84 36 0 2 0 73 0 15 41 0 1 4 39 43 266 75 60 0 0

Y 0 36 0 2 0 1 0 1 53 2 2 38 0 39 97 41 35 4 37 37

P 0 1 0 0 0 0 2 0 0 0 0 1 0 0 166 0 0 36 2 0

A 0 8 68 47 34 130 0 1 0 74 0 0 43 6 68 0 0 119 37 91

T 0 37 3 50 0 80 2 35 51 0 0 3 0 4 40 35 97 95 1 2

C 0 0 1 26 0 36 35 0 0 0 0 0 0 0 26 0 4 5 0 0

Q 0 3 0 36 1 38 36 1 3 0 24 0 1 3 4 2 39 150 13 70

G 25 7 75 39 0 0 79 0 87 2 25 3 0 37 44 3 32 41 1 39

K 0 55 49 47 29 4 36 0 0 29 0 114 81 0 7 0 47 140 394 40

S 2 103 0 5 0 4 40 110 112 96 135 5 114 42 0 0 239 5 63 111

H 0 0 0 4 2 88 4 0 2 0 2 194 0 6 2 0 33 37 0 8

N 0 160 2 43 3 2 3 0 1 8 4 32 9 90 159 10 0 151 76 124

E 1 149 1 6 4 38 2 0 3 75 0 41 159 137 39 2 85 0 9 135

R 0 43 39 2 0 1 1 0 1 54 8 2 97 236 93 0 78 49 0 58

D 4 37 2 3 39 4 76 3 2 73 1 1 125 93 122 4 123 44 4 0

Replacement residues, increasing hydrophilicity

Rep

lace

d r

esid

ues

, in

crea

sin

g h

ydro

ph

ilic

ity

Image equivalent

Lower hydrophilicity

Higher hydrophilicity

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

Tool 2: Matrix comparison

Matrix 1 Matrix 2

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

Tool 2: Matrix comparison

Matrix 1 only

Matrix 2 only

W L F I M V Y P A T C Q G K S H N E R D

Application 1: antibody engineering

FRamework

ComplementarityDeterminingRegion

Application 1: antibody engineering

CDR mutations FR mutations

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

Application 1: antibody engineering

A D R TS W

G

G

G

E

G

E

K

K

L

T

I

D

Y

R

D K IT DREngineered antibody

Application 2: vaccine design

Application 2: vaccine design

Lower hydrophilicity

Higher hydrophilicity

Application 3: biosensor design

Application 3: biosensor design

Smallerresidues

Largerresidues

Other advantages of visualization

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

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

T H A N K

Y O U ! Q

U E S T I

O N S ? ?