namedanny van noort OfficeRoom 410 building#139 (ICT) tel: webhttp://bi.snu.ac.kr/ Where to find me

Biochemistry part 1

1Introduction 2Theoretical background Biochemistry/molecular biology 3Theoretical background computer science 4History of the field 5Splicing systems 6P systems 7Hairpins 8Micro technology introductions Microreactors / Chips 9Microchips and fluidics 10Self assembly 11Regulatory networks 12Molecular motors 13DNA nanowires 14Protein computers 15DNA 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

DNARNAprotein Central dogma transcriptiontranslation

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)

Watson & Crick (1953): Nature 25: 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)

Nitrogen ous Base 34 Å Major Groove Minor Groove Central Axis Sugar-Phosphate Backbone 20 Å 5’ C 3’ OH 3’ 0HC 5’ 5’ 3’ 5’ Structure of DNA

AdenineThymine to Sugar-Phosphate Backbone to Sugar-Phosphate Backbone (+)(-) (+)(-) Hydrogen Bond GuanineCytosine to Sugar-Phosphate Backbone to Sugar-Phosphate Backbone (-) (+) (-) (+) (-) Inter-strand hydrogen bonding

20 Watson-Crick complement Inter-strand hydrogen bonding

Structure and Nomenclature of Nucleotides Nitrogenous Bases

 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

5’ 3’ PP T P A P G P C OH C 5’ 3’ Shorthand notation of a nucleic acid Structure of DNA

5’ G  T  A  A  A  G  T  C  C  C  G  T  T  A  G  C 3’ Single stranded polynucleotide

5’ G  T  A  A  A  G  T  C  C  C  G  T  T  A  G  C 3’ | | | | | | | | 3’ C  A  T  T  T  C  A  G  G  G  C  A  A  T  C  G 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

DNARNAprotein Central dogma transcriptiontranslation

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

AB a b AB ab b B a A HEAT COOL ba AB OR 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

Transcription Scientists first 3-D pictures of the "heart" of the transcription machine.

Ban et al., Science 289 ( ), 2000 Secondary Structure Of large ribosomal RNA Tertiary Structure Of large ribosome subunit Ribosomal RNA

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

Anticodon Stem D Loop TyC Loop Variable loop Anticodon Loop Secondary Structure Of large ribosomal RNA Tertiary Structure Of large ribosome subunit tRNA structure

Translation codons

Translation initiation

Translation elongation

Translation termination

Translation codons