Bioinformatics

Bioengineering Summer Camp

June 2001
Yaron Turpaz, Andrew Binkowski, Jie Liang
Outline

• Introduction
– Basic molecular biology.
• What is Bioinformatics
• UIC’s Bioinformatics group
– Research projects
– Summer camp research project.

http://gila.engr.uic.edu/bioinformatics
Gene expression = Protein production

Protein

Nucleotides
sequence

DNA
Exons & Introns

STOP F R L
Biological Diversity

Bacteria

Yeast

Fruit Fly

Human
 The Genetic Code
• From DNA sequence to Protein sequence.
• 20 Building blocks of a protein = 20 Amino acids.
From protein sequence to Structure

APRKFFVGGNWKMNGD
KKSLGELIHTLNGAKL
SADTEVVCGAPSIYLD
FARQKLDAKIGVAAQN
CYKVPKGAFTGEISPA
MIKDIGAAWVILGHSE =
RRHVFGESDELIGQKV
AHALAEGLGVIACIGE
KLDEREAGITEKVVFE
QTKAIADNVKDWSKVV
LAYEPVWAIGTGKTAT
PQQAQEVHEKLRGWLK
SHVSDAVAQSTRIIYG
GSVTGGNCKELASQHD
VDGFLVGGASLKPEFV
DIINAKH
Bioinformatics

• Computational analysis of high-throughput

biological data
– Whole genome sequencing.
– Global genomic expression & profiling.
– Functional genomics.
– Structural genomics/proteomics
– Comparative genomics.

http://gila.engr.uic.edu/bioinformatics
Bioinformatics in BioE

• Interdisciplinary approach
– Computer science, Mathematics & Statistics.
– Molecular biology, Biochemistry & Medicine.

• Rapid growing impact area of BioE:

– Boston U, UCBerkeley, UCSD, Rice, WashU, MIT,..

http://gila.engr.uic.edu/bioinformatics
 Research
• Structural genomics/proteomics
– Structural basis of functional motifs in protein families.
– The CAST server - http://cast.engr.uic.edu/
– Drug discovery.
• Functional genomics
– Collaboration with TIGR - http://www.tigr.org/
• Data mining of microbial DNA sequences for detection of foreign
DNA.
• Whole genome comparative studies.
• Gene expression analysis
– Collaboration with cancer biologist (Dr. Westbrook, School of Medicine)
• Molecular based informatics method to facilitate diagnosis of
cancer.
Gene expression
Computational analysis of
cDNA microarray expression profiles
~26,000 genes in one experiment
Functional correlation in clusters
•Genes with similar expression patterns may participate in the
same pathway or may be co-regulated.
•Clustering of expression patterns may reveal such relationships.

1. Cell division
2. cell signaling/cell communication
3. cell structure/motility
4. cell/organism defense
5. gene/protein expression
6. metabolism
7. unclassified
 Research – structure & function
How Proteins Interfaces with Other Molecules
• Analysis of protein topographic surfaces:
– Identify protein function.
– Predicting binding specificity and affinity.
– Discovery of functional similarity.

• Protein interaction with cosolvents

– Stabilization of protein solution for longer

shelf life.
– Molecular mechanism and optimization.
Structural genomics/proteomics
• Atlas of Topographic Surfaces of All Known Protein Structures
– Automatic identification of binding pockets.
– Measurement size of surface binding pockets.
• Drug Discovery
– Quantifying ligand accessibility.
– Constructing precise negative imprint or cast of binding site.
Geometry based approach for functional motifs
Voronoi Diagram and Delaunay Triangulation

Discrete Flow
3D alpha shapes (HIV-1 protease)
 What is an algorithm?

• Precisely defined procedure for

accomplishing a task.
– driving directions,
– furniture assembly instructions,
– computer programs.
• Built in hardware: fast
• Built in software
Are computers fast enough?

• NP-complete problems:
eg. Traveling salesman problem:
20 cities a few seconds
30 cities a few hours
60 cities a few decades
• Computer speed does not increase
exponentially.
Pockets in Ribonuclease A
CASTp
A Server for Identification of Protein Pockets & Cavities

Users of CASTp:
Columbia, Harvard, Mayo Clinic,
Princeton, Stanford, U Penn,
SUNY Stony Brook, Texas A&M,
UCIrvine, UBC, Virginia Tech, Yale,
Abbott Lab, Pfizer, SmithKline
Beecham, ...
Agouron, Emisphere, Vertex, ...
Kyoto U, Cambridge, European
Molecular Biology Lab,
INRA (France), Pasteur-Lille, Uppsala,
Weizman,...
Brazil, Czech, Korea, Turkey, ...

http://cast.engr.uic.edu/
CASTp Results
Calculations:
• Identifies all pockets and cavities. 
• Measures the volume and area analytically. 
• The number, area, and circumcircles of the mouth openings
for each pocket. 
Files via email:
• pocket and mouth information file,
• Pocket and mouth atoms,
• a script file for visualization using rasmol.  

http://cast.engr.uic.edu/
THANK YOU