CISC841, F08, Lec2, Liao CISC 841 Bioinformatics (Fall 2008) A Primer on Molecular Biology & Bioinformatics challenges.

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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

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

The rules for base pairing (Watson-Crick base pairing) : A with T: the purine adenine (A) always pairs with the pyrimidine thymine (T)purinepyrimidine C with G: the pyrimidine cytosine (C) always pairs with the purine guanine (G)

CISC841, F08, Lec2, Liao

C- terminal N-terminal Polypeptide

CISC841, F08, Lec2, Liao

Helix complete turn every 3.6 AAs Hydrogen bond between (-C=O) of one AA and (-N-H) of its 4 th 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

Gene Structure

CISC841, F08, Lec2, Liao

Genetic Code: codons

Systems Biology Regulatory networks Signaling transduction networks Metabolic pathway networks CISC841, F08, Lec2, Liao

Regulation Other Cells Genes (DNA) Message (RNA) Proteins Function/ Environment Regulation

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 P1lacIP2lacZlacYlacA P1lacIP2lacZlacYlacA ++++ P1lacIP2lacZlacYlacA +++ lacI protein suppressed RNA polymerase lacI LAC 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

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

Expression Profiles Classification

CISC841, F08, Lec2, Liao

Bioinformatics data sources CISC841, F08, Lec2, Liao

Bioinformatics challenges CISC841, F08, Lec2, Liao