intro domains cb1 introstruc2 lecture: protein prediction ... · 7. transfer rna (in pink) and...

title: Intro domainsshort title: cb1_introstruc2

lecture: Protein Prediction 1 - Protein structure Computational Biology 1 TUM summer 2014

Wednesday April 23, 2014

Announcements

Videos: YouTube / www.rostlab.orgTHANKS : Tim Karl + Jonas ReebSpecial lectures:

• Apr 15 - Andrea Schafferhans

No lecture:• Apr 17/22 Easter• May 01 Thu May day• May 06 Tue Student assembly• May 29 Thu Ascension day• Jun 10 Tue Whitsun holidays• Jun 19 Thu Corpus Christi

LAST lecture: July 1Examen: July 3/8

• Makeup: Oct 21 - morning

CONTACT: Lothar Richter [email protected]

TimKarl

LotharRichter

JonasReeb

TOC today

LAST week (tuesday)Protein introduction• amino acids• protein structure• bonds & energiesthis lecture (thursday)• protein domainsNEXT WEEK (tuesday)• structure comparison

3Wednesday April 23, 2014

Reality and images

Marco Punta contributed the slides

PhD in Trieste (MD for membrane proteins)Postdoc @ Columbia Univ in the City of New York (contact predictions)Senior scientist in NYCOMPS (Target selection for membrane proteins) IAS Fellow @ TUMProject manager @ Pfam @ Sanger Inst. Hinxton (Cambridgeshire)

Shapers and Shakers

Georges Braque - Houses at L'Estaque

7slide context © Marco Punta TUMWednesday April 23, 2014

Where is that?

Illustration by David S. Goodsell, the Scripps Research Institute, UCSD, USA

Mycoplasma genitalium

Protein synthesis (labels in black)1. DNA2. DNA polymerase3. single-stranded-DNA binding protein (protects single-stranded portions during replication)4. RNA polymerase5. messenger RNA6. ribosome7. transfer RNA (in pink) and elongation factor Tu (in blue)8. elongation factor Tu and Ts9. elongation factor G10. aminoacyl-tRNA synthetases11. topoisomerases12. Rec system for DNA repair: a) RecA, b) RecBC13. chaperonin GroEL (helps folding of new proteins)14. proteasome ClpA (destroys old proteins)

Enzymes for energy production (labels in red)15. glycolytic enymes16. pyruvate dehydrogenase complex

Membrane proteins (labels in blue)17. ATP synthase18. secretory proteins19. sodium pump20. zinc transporter21. magnesium transporter22. ABC transporter (different ABC transporters transport different types of molecules-ABC is short for "ATP-binding cassette")23. magnesium transporter24. lypoglycan (long carbohydrate chains connected to lipid in the membrane)

Eukaryotic cell

PLANT cell ANIMAL cell

Doyle et al. (1998) Science 280:69-77 - The structure of the potassium channel: molecular basis of K+ conduction and selectivity

http://www.proteopedia.org/wiki/images/7/7b/1htb2.png

Alcohol dehydrogenase (ADH)

PC Sanghani, H Robinson, WF Bosron, TD Hurley (2002) Biochemistry 41:10778-86

http://upload.wikimedia.org/wikipedia/commons/thumb/a/a5/Protein_ADH5_PDB_1m6h.png/800px-Protein_ADH5_PDB_1m6h.png

homodimer ADH5

Umberto Boccioni - Dynamism of a soccer player

Photograph: Filippo Monteforte/AFP/Getty Images

Different levels of abstraction

Wu et al. unpublished

Photograph: Filippo Monteforte/AFP/Getty Images

“components” of protein structure:

domains

Domain from introns?

RNA splicing

Gene product = protein

domais = introns?

Domain merger

prokaryote P, protein Aprokaryote P, protein B

prokaryote P2, protein C

Domains

3D modules

Multiple 3D alignment identfies consensus secondary structure

Guessing domains from sequence

protein Aprotein Bprotein Cprotein Dprotein Eprotein F

domain 1 domain 2

Problem: biology is not that simple

REALITYDREAM

Domain length distribution

31J Liu & B Rost (2003) Current Opinion Chem Biol 7, 5-11Wednesday April 23, 2014

some common assumptions and

facts about proteins

Some facts about proteins

how many in human?

how many in human?• 20-25K in human

how many in human?• 20-25K in humanhow long are they?

how many in human?

how many in human?• 20-25K in humanhow long are they?• ~35-30k, median around 400

how many in human?• 20-25K in humanhow long are they?• ~35-30k, median around 400do they consist of units?

protein “units”/

domains

Facts about proteins & domains

prokas=prokaryotic proteins / eukas: eukaryotic proteins

Longer proteins are rarer than shorter ones?

Prokas shorter than eukas?

Longer proteins are rarer than shorter ones? yes

Prokas shorter than eukas? yes

Kingdoms similar in length

J Liu. & B Rost (2001) Prot. Sci. 10, 1970-1979.B Rost (2002) Curr Op Struct Biol, 12, 409-416 39

Kingdoms similar in length

J Liu. & B Rost (2001) Prot. Sci. 10, 1970-1979.B Rost (2002) Curr Op Struct Biol, 12, 409-416 39

Some proteins are multi-domain, most are not

Most proteins are multi-domain?

Most proteins multi-domain

41Liu, Hegyi, Acton, Montelione & Rost 2003 Proteins 56:188-200Liu & Rost 2004 Proteins 55:678-686Wednesday April 23, 2014

42Liu, Hegyi, Acton, Montelione & Rost 2003 Proteins 56:188-200Liu & Rost 2004 Proteins 55:678-686

Single-domain proteins:61% in PDB28% in 62 proteomes

Some proteins are multi-domain, most are not no

Most proteins are multi-domain? yes

There are more proteins with 3 domains than with 1? ?

There are more proteins with 3 domains than with 1? yes

Do prokas have more domains than eukas?

Do prokas have more proteins with very many domains eukas?

Prokaryotes and eukaryotes similar

46Liu, Hegyi, Acton, Montelione & Rost 2003 Proteins 56:188-200Liu & Rost 2004 Proteins 55:678-686

Average domain length• in proteins ≥ 2 domains: ~100 residues• in proteins with 1 domain: 1.7-3 times longer

There are more proteins with 3 domains than with 1? yes

Do prokas have more domains than eukas? no

Do prokas have more proteins with very many domains eukas? yes

Target selection

Grouping is biology

how many in human?

how many in human?• 20-25K in humanhow long are they?• ~35-30k, median around 400do they consist of units?• most proteins have more than 2 domains

how many in human?• 20-25K in humanhow long are they?• ~35-30k, median around 400do they consist of units?• most proteins have more than 2 domainshow many proteins known?

how many in human?

Databases explode!

B Rost (2004) unpublished 53Wednesday April 23, 2014

Databases explode!

B Rost (2004) unpublished 53Wednesday April 23, 2014

Gap sequence/annotation grows!

>52 million protein sequences known by spring 2014

Gap sequence/annotation grows!

>52 million protein sequences known by spring 2014

double: 18 months

how many in human?

how many in human?• 20-25K in humanhow long are they?• ~35-30k, median around 400do they consist of units?• most proteins have more than 2 domainshow many proteins known?• over 50 million (109 !! doubling every 18 months!)

how many in human?• 20-25K in humanhow long are they?• ~35-30k, median around 400do they consist of units?• most proteins have more than 2 domainshow many proteins known?• over 50 million (109 !! doubling every 18 months!)prokaryotes and eukaryotes use same amino acids?

Kingdoms similar in amino acids usage

J Liu. & B Rost (2001) Prot Sci 10, 1970-1979.B Rost (2002) Curr Op Struct Biol, 12, 409-416 57

how many in human?

how many in human?• 20-25K in humanhow long are they?• ~35-30k, median around 400do they consist of units?• most proteins have more than 2 domainshow many proteins known?• over 50 million (109 !! doubling every 18 months!)

how many in human?• 20-25K in humanhow long are they?• ~35-30k, median around 400do they consist of units?• most proteins have more than 2 domainshow many proteins known?• over 50 million (109 !! doubling every 18 months!)prokaryotes and eukaryotes use same amino acids?

how many in human?• 20-25K in humanhow long are they?• ~35-30k, median around 400do they consist of units?• most proteins have more than 2 domainshow many proteins known?• over 50 million (109 !! doubling every 18 months!)prokaryotes and eukaryotes use same amino acids?• yes, except for Selenocysteine cysteine

how many in human?• 20-25K in humanhow long are they?• ~35-30k, median around 400do they consist of units?• most proteins have more than 2 domainshow many proteins known?• over 50 million (109 !! doubling every 18 months!)prokaryotes and eukaryotes use same amino acids?• yes, except for Selenocysteine cysteine... but you can predict organism from AAs

short insert:CHOP - domain

guessing

CHOP proteins into structural domains

J Liu & Rost 2004 Proteins 55:678-686

CUT 1:3D domains

CUT 2:Pfam regions

CUT 1:3D domains

CUT 2:Pfam regions

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

Final 3D done

3 target domains

CUT 1:3D domains

CUT 2:Pfam regions

CUT 1:3D domains

CUT 2:Pfam regions

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

Final 3D done

3 target domains

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

Final 3D done

3 target domains

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

Final 3D done

3 target domains

CUT 1:3D domains

CUT 2:Pfam regions

CUT 1:3D domains

CUT 2:Pfam regions

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

CUT 1:3D domains

CUT 2:Pfam regions

Final 3D done

4 target domains

CUT 3: SWISS-PROT

CUT 1:3D domains

Final5 domains “today”

CUT 1:3D domains

CUT 2:Pfam regions

CUT 1:3D domains

CUT 2:Pfam regions

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

CUT 1:3D domains

CUT 2:Pfam regions

CUT 1:3D domains

CUT 2:Pfam regions

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

CUT 1:3D domains

CUT 2:Pfam regions

CUT 3: SWISS-PROT

Lecture plan (CB1: Structure)-generic01: 2014/04/08 Tue: sorry02: 2014/04/10 Thu: welcome: who we are03: 2014/04/15 Tue: Intro 1 - acids/structure (Andrea Schafferhans)04: 2014/04/17 Thu: SKIP: Easter vacation05: 2014/04/22 Tue: SKIP: Easter vacation06: 2014/04/24 Thu: Intro 2 - domains07: 2014/04/29 Tue: Intro 3 - 3D comparisons 08: 2014/05/01 Thu: SKIP: “May day” - (NOT to be confused with “m’aidez”)09: 2014/05/06 Tue: SKIP: student assembly (SVV)10: 2014/05/08 Thu: Alignment11: 2014/05/13 Tue: Comparative modeling 112: 2014/05/15 Thu: Comparative modeling 213: 2014/05/20 Tue: Experimental structure determination14: 2014/05/22 Thu: 3D -> 1D: Secondary structure assignment15: 2014/05/27 Tue: 1D: Secondary structure prediction 116: 2014/05/29 Thu: SKIP: holiday (Ascension Day)17: 2014/06/03 Tue: Normal mode analysis (Edda Kloppmann)18: 2014/06/05 Thu: 1D: Secondary structure prediction 219: 2014/06/10 Tue: SKIP: Whitsun holidays20: 2014/06/12 Thu: 1D: Transmembrane helix prediction21: 2014/06/17 Tue: Nobel prize symposium22: 2014/06/19 Thu: SKIP: Corpus Christi (Fronleichnam)23: 2014/06/24 Tue: 1D: Transmembrane strand prediction, solvent accessibility24: 2014/06/26 Thu: 2D prediction25: 2014/07/01 Tue: 3D prediction/wrap up26: 2014/07/03 Thu: examen, no lecture27: 2014/07/08 Tue: examen, no lecture28: 2014/07/10 Thu: no lecture

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intro domains cb1 introstruc2 lecture: protein prediction ... · 7. transfer rna (in pink) and...

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