adapted from Lehninger, Nelson & Cox – Principles of Biochemistry

informationtransfer

Waste:molecules oflow energy/high entropy

Feed:molecules of highenergy/low entropy

proteins:molecular machines

assembly oforganisedstructures

adapted from Nelson – Biological Physics

order created via energy throughput in a dissipative system:sand ripples created by wind

adapted from Nelson– Biological Physics

A “simple” cell: E. coli(artist’s rendering after structural/microscopy data)

adapted from Lehninger, Nelson & Cox – Principles of Biochemistry

layer 4: cells and organelles

The Biological Cell j},.

layer 3: supra molecular

complexes

layer 2: macromolecules

layer 1: biomolecules

nucleotides N~

---- f o)y! -o-p-o-cko~

A si;-fil

protein

amino acids

protein

nucleic acids(DNA, etc.)

lipid

polysaccharide

adapted from Phillips et al. – Physical Biology of the Cell

... only four classes ofbiomolecules!

adapted from Phillips et al. – Physical Biology of the Cell

Two “polymer languages”are important in biology

adapted from Phillips et al. Physical Biology of the Cell

Translationbetween the“polymer languages”:The Genetic Code

adapted from Phillips / Kondev / Theriot – Physical Biology of the Cell

adapted from Phillips et al. – Physical Biology of the Cell

model building in biophysics:biological cartoons representidealizations of different aspectsof relevance in different contexts

cell volume VE coli 1 μm3

cell mass mE coli 1 pg

repl cycle time tE coli 3,000 s

surface area AE coli 6 μm2

genome length NE coli 5×106 bp

swimming speed vE coli 20 μm/s

E. coli adapted from Phillips et al. – Physical Biology of the Cell

biology by numbers:

order-of-magnitudeestimates are essentialfor model building!

length per bp lbp 0.34 nm

volume per bp Vbp 1 nm3

charge density per unit length λDNA 2 e/0.34 nm

persistence length ξDNA 50 nm

double-stranded DNA

typical diameter dprotein 4–5 nm

typical volume Vprotein 25 nm3

avrg. mass of AA MAA 100 Da

typ. protein mass Mprotein 30 kDa

protein conc in cell cprotein 300 mg/mL

diffusion const in water Dprotein 100 μm2/s

amino acids and proteins

dipole moment: e•r = 1.85 D (1 D = 3.33 x 10–30 Cm)→ water dielectric constant ε ~ 80 (room temp)→ boiling point: TB = 373 K (extraordinarily high!)

→

dipole moment: e•r = 0.97 D→ boiling point: TB = 213 K

→

adapted from Nelson– Biological Physics

COOH I

H2N- C- H I

alanine (A) CH3

COOH I

H2N-C-H I

CH3-CH I

valine M CHa

COOH I

H2N-C-H I

H-C-CHa I

isoleucine ?Hz (I) CH3

COOH proline (P) .... Jt!

H2C NH I I

HzC--CHz

COOH I

H2N- C-H

glycine (G) A

COOH I

H2N-C-H I

serine (S) CHzOH

COOH I

H2N-C-H I

H-C-OH I

threonine (T) CHa

COOH I

H2N-C-H I

cysteine (C) ?Hz SH

COOH I

H2N-C-H

tyrosine M ~~ y OH

COOH I

H2N-C- H I

tryptophane ?Hz 0/V) C=CH

b"

COOH I

H2N-C-H I

aspartic CHz

acid(D) booH

COOH I

H2N-C-H I

CH2 I

glutamic CHz

acid (E) booH

COOH I

H2N-C-H I

histidine (H) . b~~H II PH

HC..._Nor

COOH I

H2N-C-H . I

asparag1ne CH2

(N) I "'c.....___

0 "' NHz

COOH I

HzN-C- H I

phenylalanine

6CHz

(F) ~ I

'

COOH I

H2N-C-H I

arginine ?Hz (R) CHz

I CHz I

NH I C=NH I

NHz

COOH I

H2N-C-H

tHz I CH2 I

lysine (K) CHz I CHz I

NHz

COOH I

H2N-C-H

th. . I

me 1omne CH2

. (M) I CHz

~ I CHa

COOH I

H2N- C- H I

glutamine ?Hz

(Q) CHz I

"'c o"' NHz

adapted from Nelson– Biological Physics

hydrogen bond 0.177 nm

covalent bond 0.0965 nm

adapted from Alberts et al. –Molecular Biology of the Cell

limitations to dihedral angles: Ramachandran diagram

adapted from Jackson– Molecular & Cellular Biophysics

example:bacteriorhodopsin, a membrane-bound converter for light into electrical energy

“free” water:high disorder – tumbling motion, yet many H bondsH bonds may form in many mutual orientations – entropy large

water near hydrophilic headgroup:same structure as in “free “ water

water near hydrophobic tail:highly ordered water: low entropy

lipid aggregation in water

entropy decrease for lipids,but larger entropy increase for water

entropy decrease for lipids,but larger entropy increase for water

adapted from Alberts et al. –Molecular Biology of the Cell

lipid molecule protein molecules

adapted from Lehninger, Nelson & Cox – Principles of Biochemistry

lipid/proteinmembranes

adapted from Alberts et al. –Molecular Biology of the Cell

proteins with differentproperties (e.g., shorttransmembrane span)

can’t enter raft → selectivity!

adapted from Alberts et al. –Molecular Biology of the Cell

MD simulation: D. Tobias, UC Irvineadapted from Nelson – Biological Physics

adapted from Alberts et al. –Molecular Biology of the Cell

o-o ...... , 0 'p-0

O~p- -\ _0/ \ , 0 o:R

/ 0 O =P-0-

\ hydrogen bond 5' end 3'end

0 \

P=O cf 'o- l

0.34 nm

phosphodiester bond

J

adapted from Alberts et al. –Molecular Biology of the Cell

H

0 IIIIH-N1

H

N ~ rN H

1N-H i1111 0 y

n,;no• g.ooVO /

T1'aior groove T1'aior groove

H I

CH3 0 111\IH-N N~

"-- n,;no, g.oo<'

H I

/C~ /CH3 N C I I thymine

c c 0~ ""'-N/ ~0

I -H

II N"" ~c,

C N I // N // adenine -- c

"---H

"'

5'

cytosine

...-:::C t. _ Ac, 0/" ~ " N-H

I H H H

I I /N"-. / N '- -::/0\

H C C hydrogen 11 1 bond

sugar-phosphate backbone

adapted from Alberts et al. –Molecular Biology of the Cell

adapted from Lehninger, Nelson & CoxPrinciples of Biochemistry

1st

lett

er

of

codon

2nd letter of codon

adapted from Lehninger, Nelson & Cox – Principles of Biochemistry and from Alberts et al. – Molecular Biology of the Cell

tRNA

phosphoanhydride bonds

~ ~ o- o- o -1 I I

-o-P-0-P-0-P

energy in ,.. photosynthesis,

food , ...

o-1

-o-P-OH + II 0

II II II 0 0 0

o- o-1 I -o-P -0-P - 0-CH II II 2

0 0

energy out ,.. chemical synthesis,

motility, ... (almost anything

that requires energy in the cell!)

many isomers possible!

myriads of differentstructures possible!

GlcNAc: N-acetyl glucosamineMurNAc: N-acetyl muraminic acid

adapted fromLehninger, Nelson & Cox

Principles of Biochemistry