name danny van noort

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email danny@bi.snu.ac.kr

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Biochemistry part 1

1 Introduction

2 Theoretical backgroundBiochemistry/molecular biology

3 Theoretical backgroundcomputer science

4 History of the field

5 Splicing systems

6 P systems

7 Hairpins

8 Micro technology introductions Microreactors / Chips

9 Microchips and fluidics

10 Self assembly

11 Regulatory networks

12 Molecular motors

13 DNA nanowires

14 Protein computers

15 DNA computing - summery

Course outline

Popular books

More popular books

Very short introduction

ATOM

MOLECULE

CELL

ORGANISM

SPECIES

Physical

Chemical

Biological

Physiological

Ecological

Biological background

Role of molecules in cells

Perform various chemical reactions necessary for

life => diverse 3D structures necessary

Pass on the instructions for making an organism

=>simple 1D medium sufficient

Types of molecules in cells

Proteins: 3D structures

DNA: 1D medium

RNA: intermediary between DNA and proteins

Molecular biology concepts

Cells

Humans

60 trillion cells

320 cell types

Classified into two types:

Eukaryotes contain a membrane-bound nucleus and

organelles (plants, animals, fungi,…)

Prokaryotes lack a true membrane-bound nucleus and

organelles (single-celled, includes bacteria)

Not all single celled organisms are prokaryotes!

Organisms

• In eukaryotes, nucleus contains one or several double

stranded DNA molecules organized as chromosomes

• Humans:

– 22 Pairs of autosomes

– 1 pair sex chromosomes

Chromosomes

Chromosomes

DNA RNA protein

Central dogma

transcription translation

deoxyribonucleic acid

The sequence of the human genome

has 2.91 billion base pairs (bp)

and approximately 35,000 genes.

(last count 2003)

DNA (deoxyribonucleic acid)

DNA (deoxyribonucleic acid)

Watson & Crick (1953): Nature 25: 737-738

Molecular Structure of Nucleic Acids: a

structure for deoxyribose nucleic acid.

Nobel Prize, 1962.

Nucleotide: purine or pyrimidine base deoxyribose sugar phosphate group

Purine bases A(denine), G(uanine)

Pyrimidine bases C(ytosine), T(hymine)

DNA (deoxyribonucleic acid)

Nitrogenous Base

34 Å

MajorGroove

Minor Groove

Central Axis

Sugar-PhosphateBackbone

20 Å 5’ C 3’ OH

3’ 0H C 5’

5’

3’

3’

5’

Structure of DNA

Adenine Thymine

to Sugar-PhosphateBackbone

to Sugar-PhosphateBackbone

(+) (-)

(+)(-)

Hydrogen Bond

Guanine Cytosine

to Sugar-PhosphateBackbone

to Sugar-PhosphateBackbone

(-) (+)

(+)(-)

(+)(-)

Inter-strand hydrogen bonding

20

Watson-Crick complement

Inter-strand hydrogen bonding

Structure and Nomenclature of Nucleotides

Nitrogenous Bases

N

N NH

N

NH2

HN

N NH

N

O

H2N

N

NH

NH2

O

NH

NH

O

O

NH

NH

O

O

N

N NH

N

N

N

1

2

34

56 7

8

9

1

2

34

5

6

Adenine(6-amino purine)

Guanine (2-amino-6-oxy purine)

Cytosine (2-oxy-4-amino pyrimidine)

Thymine (2-oxy-4-oxy 5-methyl pyrimidine)

Uracil(2-oxy-4-oxypyrimidine)

purine

pyrimidine

Nucleic acids are polynucleotides;

Nucleotides are linked by phosphodiester bridges from

3’ to 5’;

Polymers of ribonucleotides are ribonucleic acids, or

RNA;

Polymers of deoxyribonucleotides are deoxyribonucleic

acids, or DNA;

Structure of DNA

Sugar backbone

N

NN

N

NH2

O

OHO

HHHH

PO

O

O

O-

NH

N

N

O

NH2N

O

OH

HHHH

O

PO

-O

O-

5’

3’

P P

T

P

A

P

G

P

C

OH

C

5’

3’

Shorthand notation of a nucleic acid

Structure of DNA

5’ GTAAAGTCCCGTTAGC 3’

Single stranded polynucleotide

5’ GTAAAGTCCCGTTAGC 3’| | | | | | | | | | | | | | | |3’ CATTTCAGGGCAATCG 5’

Double stranded polynucleotide

27

The B-form is the common

natural form, prevailing

under physiological

conditions of low ionic

strength and high degree

of hydration.

The Z-form (Zigzag chain)

is observed in DNA G-C

rich local region.

The A-form is sometimes

found in some parts of

natural DNA in presence

of high concentration of

cations or at a lower

degree of hydration

(<65%).

Structure of DNA

Central dogma

DNA RNA protein

Central dogma

transcription translation

Replication of DNA

Replication of DNA

Replication of DNA

During replication, the DNA helix is unraveled and its two

strands are separated. An area known as the replication

bubble forms and progresses along the molecule in both

direction. Then each DNA strand serves as a template for the

synthesis of a new complementary strand.

Each daughter DNA molecule is an exact copy of its parent

molecule, consisting of one old and one new DNA strand. Thus

the replication is semi-conservative

A B

a b

A B

a b

b

B

a

A

HEAT

COOL

ba

A BOR

100° C

Strand hybridisation

’ ’

’ ’

Ligase joins 5' phosphate to 3' hydroxyl

’ ’

DNA ligation

EcoRI

HindIII

AluI

HaeIII

- OH 3’

5’ P -

- P 5’

3’ OH -

Restriction endonucleases

DNA polymerase

ribonucleic acid

Similar to DNA

Thymine (T) is replaced by uracil (U)

Forms secondary or tertiary structures

RNA can be:

Single stranded

Double stranded

Hybridized with DNA

RNA (ribonucleic acid)

Types of RNAs:

Transfer RNA (adaptor molecule)

Messenger RNA (template for protein synthesis)

Ribosomal RNA (protein synthesis)

Small nuclear RNA (splicesomal RNA)

Small nucleolar RNA (ribosomal RNA processing)

Interference RNA (gene silencing)

microRNA (translation regulation)

Virus RNA (code virus genome)

In comparison with DNA structures, much less is known

about RNA structures. Most RNA are associated with

proteins which facilitate their structural folding.

RNA (ribonucleic acid)

RNA secondary structure

Messenger RNA

Linear molecule encoding genetic information

copied from DNA molecules

Transcription: process in which DNA is copied

into an RNA molecule

mRNA

Eukaryotic genes can be pieced together

Exons: coding regions

Introns: non-coding regions

mRNA processing removes introns, splices

exons together

Processed mRNA can be translated into a

protein sequence

mRNA processing

Parts List:

mRNA is template

tRNA

ribosomes

amino acids

aminoacyl tRNA transferases

mRNA processing

mRNA processing

Transcription

Scientists first 3-D pictures of

the "heart" of the transcription

machine.

Ban et al., Science 289 (905-920), 2000

Secondary StructureOf large ribosomal RNA

Tertiary StructureOf large ribosome subunit

Ribosomal RNA

Translation

Translation

Transfer RNA

Well-defined three-dimensional structure

Critical for creation of proteins

tRNA

Amino acid attached to each tRNA

Determined by 3 base anticodon sequence (complementary

to mRNA)

Translation: process in which the nucleotide sequence

of the processed mRNA is used in order to join amino

acids together into a protein with the help of

ribosomes and tRNA

tRNA

tRNA structure

AnticodonStem

D Loop

TyC Loop

Variableloop

Anticodon Loop

Secondary Structure Of large ribosomal RNA

Tertiary StructureOf large ribosome subunit

tRNA structure

Translation codons

Translation initiation

Translation elongation

Translation termination

Translation codons