PROTEIN PHYSICSPROTEIN PHYSICS

LECTURE 1LECTURE 1

Introduction & overviewIntroduction & overview

GlobularGlobularproteinsproteins

Fibrous proteinsFibrous proteins

H-bonds (NH:::OC)H-bonds (NH:::OC) & & hydrophobic forceshydrophobic forces

MembraneMembraneproteinsproteins

Protein chainProtein chain(gene-encoded (gene-encoded sequence) sequence)

Secondary structures (Secondary structures (-helices-helices, , -strands-strands) ) are most conserved structural elements. are most conserved structural elements. They form a basis of protein classificationThey form a basis of protein classification

One protein - various One protein - various crystallization, NMRcrystallization, NMR

Homologous Homologous (closely related) (closely related)

proteinsproteins

PROTEIN HAS DEFINITE 3D STRUCTUREPROTEIN HAS DEFINITE 3D STRUCTURE

Globular proteinsGlobular proteins

Fibrous proteinsFibrous proteins

H-bonds (NH:::OC)H-bonds (NH:::OC) & & hydrophobic forceshydrophobic forces

MembraneMembraneproteinsproteins

SequenceSequence & & StructureStructure

GlobularGlobulardomainsdomains

CCAATTHH

PROTEIN CHAINPROTEIN CHAINCAN FORM ITS UNIQUE 3D STRUCTURE CAN FORM ITS UNIQUE 3D STRUCTURE

SPONTANEOUSLYSPONTANEOUSLYIN VITROIN VITRO

BIND BIND TRANSFORM TRANSFORM RELEASE RELEASE:: ENZYMES ENZYMES (chymotrypsin)(chymotrypsin)

Note small active siteNote small active site

POST-TRANSLATIONAL MODIFICATIONSPOST-TRANSLATIONAL MODIFICATIONSSometimes,Sometimes,

CHAIN CUT-INDUCED DEFORMATIONCHAIN CUT-INDUCED DEFORMATION MAKES ENZYME ACTIVEMAKES ENZYME ACTIVE

Chymotripsin ChymotripsinoChymotripsin Chymotripsinogengen

active active cat. sitecat. site

non-non-active active cat. sitecat. site

POST-TRANSLATIONAL MODIFICATIONS:POST-TRANSLATIONAL MODIFICATIONS:(especially in eukaryotes):(especially in eukaryotes):

PROTEIN CHAIN CUTS (proteolysis),PROTEIN CHAIN CUTS (proteolysis), - SPLICING (inteins) - SPLICING (inteins) - CYCLIZATION - CYCLIZATION - INTERNAL CHEM. TRANSFORMATION - INTERNAL CHEM. TRANSFORMATION

GLYCOSYLATION, etc. GLYCOSYLATION, etc.

MODIFICATION OF ENDS (acetylation, etc.)MODIFICATION OF ENDS (acetylation, etc.)

MODIFICATION OF SIDE CHAINS (S-S bonding,MODIFICATION OF SIDE CHAINS (S-S bonding, phosphorilation, etc.) phosphorilation, etc.)

COFACTORS …COFACTORS …

SometimesSometimes::

Different folds with the same active site: Different folds with the same active site: the same biochemical functionthe same biochemical function

SometimesSometimes::

Similar folds with different active sites: Similar folds with different active sites: different biochemical functiondifferent biochemical function

4-helix bundle

COFACTORS: HEME, 2Fe, RNA, …

Standard positions of active sites Standard positions of active sites in protein foldsin protein folds

PROTEIN PHYSICSPROTEIN PHYSICS

LECTURE 2LECTURE 2

Elementary interactions:Elementary interactions:covalentcovalent

Protein chainProtein chain::

regular backboneregular backbone&&

gene-encoded sequencegene-encoded sequenceof side chains of side chains

Protein chainProtein chain

Covalent bond Covalent bond lengths:lengths:

0.9 – 1.8 0.9 – 1.8 ÅÅ

Covalent bond Covalent bond angles:angles:

109109oo – 120 – 120oo

Atom radii:Atom radii:1 – 2 1 – 2 ÅÅ

Side Side

chainschains

Main-chainMain-chainpeptide group: peptide group: flat & rigidflat & rigid

Side Side chains: chains:

L-L-amino amino acidsacids

______

Protein chainProtein chain

____________ ____________

Ala Ala __LL

GlyGly

ThrThr

IleIle

TwoTwoasymmetricasymmetric side side chains:chains:

asymmetricasymmetricbackbone- backbone- side_chain:side_chain:

Peptide group: Peptide group: flat & rigidflat & rigid

sp2sp2 + + pp sp2sp2 + + pp

Covalent bondingCovalent bonding

Main-chain:Main-chain:N-CN-C))(C(C-C’),-C’),

(C’=(C’=N)N)

Side-chain:Side-chain:

CountingCountingangles: angles:

__________________________________________________________________________________________00oo180o

120o

sp2 - sp2 (sp2 - sp2 () )

= 180= 180o o = 0 = 0oo

Potentials: from IR spectra of vibrations Potentials: from IR spectra of vibrations

sp2 - sp2 (sp2 - sp2 () )

sp3 – sp3 (sp3 – sp3 () )

sp2 – sp3 (sp2 – sp3 () )

Pro Pro

All,All,but Probut Pro

CHCH33-CH-CH33 C-CHC-CH22-CH-CH22-C-C

__________________________________________________________________________________________classical