DNA -> RNA -> Proteins

• Proteins are central to life

• Cellular structure, communications, etc.

• Medical, drug development

• Failure -> disease (ex: missing, misfolding)

• The key to protein function is structure

Structure Representation (Protein)

CPK: hard sphere model Ball-and-stick Cartoon

Patrice Koehl

Proteins

Sequence

QKPFQCRICM

RNFSRSDHLT

THIRTHTG

>7million sequences

Structure

65,000 structures

From Sequence to Function and Back…

KKAVINGEQIRSISDLHQTLKKWELALPEYYGENLDALWDCLTGVEYPLVLEWRQFEQSKQLTENGAESVLQVFREAKAEGCDITI

Sequence

Structure

Function

Evolution

ligand

The Cycle of Life

Patrice Koehl

Protein: Linear chain of amino acidscalled residues (4 in this toy protein)

Ser

Trp

Leu

O

NN N

N

O O

CCCC

O

OCα

CαCα Cα

Lys

HH

H H

H

The backbone (red) is the same for all residues. The side-chains (green) vary.

Polar Amino acids

C

CH2

CH2

C

CA

CB CG

CDNE2

NH2OOE1

GlutaminePatrice Koehl

C

CH2

C

CH CH

CH CH

C

CA

CB

CGCD1

CE1

CZCE2CD2

OH

OH

Polar Amino acids

Patrice Koehl

Tyrosine

How a Protein Takes Shape

Patrice Koehl, UC Davis, http://koehllab.genomecenter.ucdavis.edu/teaching

Energy Landscape

Unfolded StateExpanded, disordered Molten Globule

Compact, disordered

Native StateCompact, Ordered

BarrierHeight

1 ms to 1s

1 s

Barrier crossing time~ exp[Barrier Height]

Patrice Koehl

Some applications of Bioinformatics

• Find genes

• Predict protein docking

• Protein design: drug development

• Cancer

• Flu

Interface: 1AKJ ligand (green) and receptor (blue):

Protein Docking

Protein design

Engineer to bind to radioactive isotope

What Is Cancer?

Loss of Normal Growth Control

Cancer cell division

Fourth orlater mutation

Third mutation

Second mutation

First mutation

Uncontrolled growth

Cell Suicide or Apoptosis

Cell damage—no repair

Normal cell division

Example of Normal Growth

Cell migration

Dermis

Dividing cells in basal layer

Dead cells shed from

outer surface

Epidermis

The Beginning of Cancerous Growth

Underlying tissue

Tumors (Neoplasms)

Underlying tissue

Invasion and Metastasis

3Cancer cells reinvade and grow at new location

1Cancer cells invade surrounding tissues and blood vessels

2Cancer cells are transported by the circulatory system to distant sites

Malignant versus Benign Tumors

Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize to different sites

Time

Benign (not cancer) tumor cells grow only locally and cannot spread by invasion or metastasis

What Causes Cancer?Some viruses or bacteria

HeredityDiet

Hormones

RadiationSome chemicals

Use Machine Learning to Detect Gene Interactions

Why find gene interactions?

• diagnosis of disease

• genes code for proteins: hope to gain knowledge of biochemical pathways in disease

Test data with different gene and gene pairs perturbed to unmutated

1. Training step: weights are adjusted to predict cancer

Test data

2. Predict step:genes 2 and 7 interact?

P0

P2, P7, P2,7

3. Apply Metric:

If (P0 - P2,7) = (P0 - P2) + (P0 - P7) then additive model, no interactions.

Viruses

• Viruses on the attac http://www.youtube.com/watch?v=Dh4C-qmfuro&NR=1

• Flu Attack! How A Virus Invades Your Body

http://www.youtube.com/watch?v=Rpj0emEGShQ&feature=related