cisc841, f08, lec2, liao cisc 841 bioinformatics (fall 2008) a primer on molecular biology &...
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CISC841, F08, Lec2, Liao
CISC 841 Bioinformatics(Fall 2008)
A Primer on Molecular Biology&
Bioinformatics challenges
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
10-310-610-9
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
DNA (double helix, hydrogen bond, complementary bases A-T, G-C) 5' end phosphate group 3' end is free 1' position is attached with the base
double strand DNA sequences form a helix via hydrogen bonds between complementary bases
hydrogen bond: - weak: about 3~5 kJ/mol (A covalent C-C bond has 380 kJ/mol),
will break when heated - saturation: - spefic:
CISC841, F08, Lec2, Liao
1
5
• Purines:A and G
• Pyrimidines: C and T
• Oligonucleotide: a DNA of a few tens of nucleotides
• ATP, ADP, AMP
3
Structure of the bases (Thymine is not shown here)
CISC841, F08, Lec2, Liao
Small molecules: > sugar: carbohydrate > fatty acids > nucleotides: A, C, G, T (Purines: A and G; Pyrimidines: C and T)
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
The rules for base pairing (Watson-Crick base pairing) : A with T: the purine adenine (A) always pairs with the pyrimidine thymine (T) C with G: the pyrimidine cytosine (C) always pairs with the purine guanine (G)
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
C- terminal
N-terminal
Polypeptide
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
• Helix complete turn every 3.6 AAs
• Hydrogen bond between (-C=O) of one AA and (-N-H) of its 4th neighboring AA
CISC841, F08, Lec2, Liao
Hydrogen bond b/w carbonyl oxygen atom on one chain and NH group on the adjacent chain
The Central Dogma:
DNA RNA Protein
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
Gene Structure
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
Genetic Code: codons
Systems Biology
• Regulatory networks
• Signaling transduction networks
• Metabolic pathway networks
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
Regulation
Other Cells
Genes(DNA)
Message(RNA)
Proteins Function/Environment
RegulationRegulation
CISC841, F08, Lec2, Liao
Operon
lac operon on E. coli
Lactose binds with lacI, allowing RNA polymerase to bind to P2 and transcribe the structural genes
P1 lacI P2 lacZ lacY lacA
P1 lacI P2 lacZ lacY lacA+ + + +
P1 lacI P2 lacZ lacY lacA+ + +
lacI protein
suppressedRNA polymerase
RNA polymerase
lacILAC
LACLAC
Repressor protein coded by lacI, bind to P2 preventing transcription of lacZ, lacY and lacA
CISC841, F08, Lec2, Liao
Boolean Networks: An example
Reverse EngineeringInterpreting data
1: induced
0: suppressed
-: forced low
+: forced high
Bayesian networks: P(0,1,2,3) = P(0)P(1)P(2|1,0)P(3|1,2)
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
High throughput technologies
• Genome sequencing
• DNA microarray
• Yeast 2 hybrid system
CISC841, F08, Lec2, Liao
Sequencing DNA (Sanger’s method)
Courtesy of Color Atlas of Biochemistry
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
Expression Profiles Classification
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
Bioinformatics data sources
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
Bioinformatics challenges
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao
CISC841, F08, Lec2, Liao