Moore s law in information technology. exponential growth!

Transcription

1 Moore s law in information technology exponential growth!

2 ... and how it compares to developments in bio sciences

3 Biology is driven by an avalanche of new information... DNA sequencing methods and throughput data from M. R. Stratton, P. J. Campbell & P. A. Futreal, Nature 458 (2009),

4 Biology is driven by an avalanche of new information... cumulative no. of solved protein structures exponential growth over 40 years!

5 transcriptional regulatory sequence (TRS) Quantification unravels new insights! Example: A biophysical investigation of protein-dna and proteinprotein interactions in the regulation of gene transcription catabolite activator protein (a.k.a. CAP) RNA polymerase Green Fluorescent Protein Kinney et al., Proc. Natl. Acad. Sci. USA 107 (2010)

6 transcriptional regulatory sequence (TRS) Quantification unravels new insights! Example: A biophysical investigation of protein-dna and proteinprotein interactions in the regulation of gene transcription binding affinity of one single protein to DNA easy to measure but how does one measure individual protein affinities in complex aggregates, as well as protein-protein interactions?... and precisely sequenced in each batch ( deep sequencing ) cells are roughly sorted according to intensity corresponding gene products: cells whose emission depend on the efficiency of gene transcription as a function of mutation of the regulatory sequence LARGE, highly mutated set of DNA strands (> 200,000) Kinney et al., Proc. Natl. Acad. Sci. USA 107 (2010)

7 Quantification unravels new insights! StatMech interpretation of mutation maps: how much does a specific mutation stabilize/destabilize protein binding? how strongly do proteins bind overall? how strongly do proteins interact with each other? information footprint : how does gene expression depend on the position of mutations? how strongly binds a regulatory protein to any location in the TRS? Kinney et al., Proc. Natl. Acad. Sci. USA 107 (2010)

8 A few numbers yield a molecular census Quantity of interest Approx. value Water Content in average cell 70 wt% Macromolecules Total cellular concentration 300 mg/ml Amino acids/proteins Cellular protein conc 150 mg/ml Mass of "average" AA Mass of "average" protein Radius of "average" protein 100 Da 30,000 Da 2 nm Volume of "average" protein 25 nm 3 Lipid bilayers Mass of lipid 800 Da Area per lipid 0.5 nm 2 E. coli Cell volume 1 μm 3 Cell mass 1 pg Cell surface area 6 μm 2 molecular census (E.coli) proteins (total) membrane proteins ribosomes lipids water ions DNA ,

9 A few numbers yield a molecular census Quantity of interest Approx. value Water Content in average cell 70 wt% Macromolecules Total cellular concentration 300 mg/ml Amino acids/proteins Cellular protein conc 150 mg/ml Mass of "average" AA 100 Da Mass of "average" protein 30,000 Da Radius of "average" protein 2 nm Volume of "average" protein 25 nm 3 Lipid bilayers Mass of lipid 800 Da Area per lipid 0.5 nm 2 E. coli Cell volume 1 μm 3 Cell mass 1 pg Cell surface area 6 μm 2 molecular census (E.coli) proteins (total) (15 wt%) membrane proteins ribosomes 20,000 RNA (total) 300,000 (6 wt%) rrna 60,000 (5 wt%) trna 200,000 (1 wt%) mrna 1,000 (<< 1 wt%) lipids (3 wt%) water (70 wt%) ions DNA 2 (1 wt%)

10 The cell interior is crowded! David Goodsell

11 Rules of thumb Quantity of interest Rule of thumb E. coli Cell volume 1 μm 3 Cell mass 1 pg Cell surface area 6 μm 2 Genome length Cell cycle time Swimming speed bp 3,000 s 20 μm/s Yeast Cell volume 60 μm 3 Cell mass Cell diameter Genome length Cell cycle time 60 pg 5 μm 10 7 bp 200 min Organelles Diameter of nucleus 5 μm Diameter of mitochondrion Diameter of transport vesicles 2 μm 50 nm Water Molecular volume 30 Å 3 Density 1 g/cm 3 Viscosity 1 centipoise (10 2 g cm 1 s 1 ) Hydrophobic energy 2,500 cal mol 1 nm 2 Surface tension 70 mn/m

12 Rules of thumb Quantity of interest Rule of thumb double-stranded DNA (dsdna) Length per base pair 1/3 nm Volume per base pair 1 nm 3 Charge density Persistence length 2 e /bp 6 e /nm 50 nm Amino acids/proteins Mass of "average" AA 100 Da Mass of "average" protein Radius of "average" protein 30,000 Da 2 nm Volume of "average" protein 25 nm 3 Cellular protein concentration Protein motor: char. force Protein motor: char. speed Diffusion constant of "average" protein in cell 150 mg/ml 5 pn 200 nm/s 10 μm 2 /s Lipid bilayers Bilayer thickness 5 nm Area per lipid 0.5 nm 2 Mass of lipid Compression modulus Bending modulus 800 Da 50 kbt/nm 2 ( 200 mn/m) 50 kbt Phillips et al., Table 1.1

13 Variance in selection processes σ (N) N Phillips et al., Fig. 2.7