COT 6930HPC and Bioinformatics

Introduction to Molecular Biology

Xingquan ZhuDept. of Computer Science and Engineering

Outline

Cell DNA

DNA Structure DNA Sequencing

RNA (DNA-> RNA) Protein

Protein structure Protein synthesis

Central Dogma of Biology: DNA, RNA, and the Flow of Information

TranslationTranscription

Replication

A sequence from 20 amino acids

Adopts a stable 3D structure that can be measured experimentally

RibbonSpace fillingCartoon Surface

Oxygen

Nitrogen

Carbon

Sulfur

Protein

Lys Lys Gly Gly Leu Val Ala His

X-ray Crystallography

X-ray Crystallography

X-ray Crystallography

The 20 amino acids

• Each amino acid contains an "amine" group (NH3) and a "carboxy" group (COOH) (shown in black in the diagram).• The amino acids vary in their side chains (indicated in blue in the diagram).

Protein Structure

Protein Structure Primary structure (amino acid sequence) Secondary structure (local folding) Tertiary Structure (global folding) Quaternary structure (multiple-chain)

Protein Structure Animation https://mywebspace.wisc.edu/jonovic/web/

proteins.html

Primary Structure

Primary structure is described by the sequence of Amino Acids in the chain

C- terminal

N-terminal

Polypeptide

One end of every polypeptide, called the amino terminal or N-terminal, has a free amino group. The other end, with its free carboxyl group, is called the carboxyl terminal or C-terminal.

Peptide: 50 amino acids or lessPolypeptide: 50-100 amino acidsProtein: over 100 amino acids

Polypeptide

The amino acids are linked covalently by peptide bonds. The image shows how three amino acids linked by peptide bonds into a tripeptide.

Secondary Structure Secondary structure describes the way the chain

folds Local structure of consecutive amino acids Common regular secondary structures

Helix Sheet b turn

Secondary Structure Alpha helix Beta strand / pleated sheet Coil

Tertiary Structure of protein

Tertiary Structure describes the shapes which form when the secondary spirals of the protein chain further fold up on themselves.

Quaternary structure (multi-chain structures)

Quaternary structure describes any final adjustments to the molecule before it can become active. For example, pairs of chains may bind together or other inorganic substances may be incorporated into the molecule.

Protein Structure Space

http://www.nigms.nih.gov/psi/

Protein folding taxonomy :

all alphaall beta

alpha/betaalpha+beta

others

Geometry of Protein Structure

rotatable rotatable

Total number of degree is 2*(n-1)

where n is the length of the protein

The Leventhal Paradox

Given a small protein (100aa) assume 3 possible conformations/peptide bond

3100 = 5 × 1047 conformations Fastest motions 10- 15 sec so sampling all conformations would

take 5 × 1032 sec 60 × 60 × 24 × 365 = 31536000 seconds in a year Sampling all conformations will take 1.6 × 1025 years Proteins do not have problem in folding, we have! the Leventhal

paradox

Outline

Cell DNA

DNA Structure DNA Sequencing

RNA (DNA-> RNA) Protein

Protein structure Protein synthesis

3 types of RNA

RNA

Messenger RNADNA: TAC CAT GAG ACT … ATC mRNA: AUG GUA CUC UGA …

UAG

Ribosomal RNA and ribosomes

Transfer RNA

Overview of protein synthesis

Transcription: same language

Translation: different language

Overview of protein synthesis

A. TranscriptionNo Thymine, instead hasUracil

2. Translation, the final steps

Rules (the secret of life) Transcription:

A →U T →A

Translation

G →C C →G

AUG: Methionine (Met)

Codons and anticodonsDNA: TAC CAT GAG ACT … ATC

mRNA: AUG GUA CUC UGA … UAGtRNA: UAC CAU GAG ACU … AUC

DNA RNA

cDNAESTsUniGene

phenotype

GenomicDNADatabases

Protein sequence databases

protein

Protein structure databases

transcription translation

Gene expressiondatabase

List of Amino Acids (1)

List of Amino Acids (2)

Transcription & Open Reading Frame (ORF)

Open Reading Frame (ORF) Where to start reading codons (ATG) 6 possible reading frames (3 forward, 3 backward) Gene is usually longest ORF found

Forward reading frame example

Complication – Non-coding Regions

Non-coding regions Very little genomic DNA produce proteins Exon – DNA expressed in protein (2–3% of human genome) Intron – DNA transcribed into mRNA but later removed Untranslated region (UTR) – DNA not expressed

UTRs may affect gene regulation & expression Biological processes

Remove introns from mRNA, splice exons together Transition between intron / exon = splice site

Splicing can be inconsistent Some exons may be skipped Result = splice-variant gene / isoform Estimated 30% of human proteins from splice-variant genes

Non-coding regions

Transcription

The process of making RNA from DNA

Needs a promoter region to begin transcription.

ExonsControl regions

Splicing

Transcription Introns

Alternative Splicing

One single gene produce different forms of a protein A single gene can contain numerous exons and introns, and the

exons can be spliced together in different ways

Complication: Mutations

Mutations Modifications during DNA replication

Possible changes Point mutation / single nucleotide polymorphism (SNP)

5’ A T A C G T A … 5’ A T G C G T A … Occur every 100 to 300 bases along the 3-billion-base human

genome Duplicate sequence Inverted sequence Insert / delete sequence ( indel )

Mutations

Mutations

Outline

Cell DNA

DNA Structure DNA Sequencing

RNA (DNA-> RNA) Protein

Protein structure Protein synthesis

Excellent Animation

Cell http://www.youtube.com/watch?

v=UB6G9GD2KFk Central Dogma

http://www.youtube.com/watch?v=GkdRdik73kU