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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 ? ?