Figure 4-1 Essential Cell Biology (© Garland Science 2010)

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2

N Cα C

OH H

R

N Cα C

OH H

R

N Cα C

OH H

R

N Cα C

OH H

R

N Cα C

OH H

R

N Cα C

OH H

R

N Cα C

OH H

R

N Cα C

OH H

R

amino acid residue hydrogen bond donor hydrogen bond acceptor

Figure 4-2 Essential Cell Biology (© Garland Science 2010)

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Figure 4-3 Essential Cell Biology (© Garland Science 2010)

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6

Figure 4-26 Essential Cell Biology (© Garland Science 2010)

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Figure 4-5 Essential Cell Biology (© Garland Science 2010)

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Figure 4-9 Essential Cell Biology (© Garland Science 2010)

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Figure 4-4 Essential Cell Biology (© Garland Science 2010)

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N Cα C

OH H

R

N Cα C

OH H

R

N Cα C

OH H

R

N Cα C

OH H

R

N Cα C

OH H

R

N Cα C

OH H

R

N Cα C

OH H

R

N Cα C

OH H

R

amino acid residue hydrogen bond donor hydrogen bond acceptor

Figure 4-6 Essential Cell Biology (© Garland Science 2010)

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13

native state

(unfolded)

aggregates

(insoluble)

unfolded protein

misfolded state

(solvent-exposed

hydrophobic groups) proteolytic

degradation

14

Figure 4-8 Essential Cell Biology (© Garland Science 2010)

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secondary tertiary quartenary

Figure 4-16 Essential Cell Biology (© Garland Science 2010)

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helixhelixloopsloops

sheetsheet

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Figure 4-10a–c Essential Cell Biology (© Garland Science 2010)

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Figure 4-10d–f Essential Cell Biology (© Garland Science 2010)

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Figure 4-14 Essential Cell Biology (© Garland Science 2010)

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Figure 4-17 Essential Cell Biology (© Garland Science 2010)

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Figure 4-19 Essential Cell Biology (© Garland Science 2010)

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Figure 4-21 Essential Cell Biology (© Garland Science 2010)

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Figure 4-22 Essential Cell Biology (© Garland Science 2010)

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Figure 4-23 Essential Cell Biology (© Garland Science 2010)

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Figure 4-24 Essential Cell Biology (© Garland Science 2010)

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Figure 4-46 Essential Cell Biology (© Garland Science 2010)

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Figure 4-47 Essential Cell Biology (© Garland Science 2010)

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PhysicsPhysics-- versus bioinformaticsversus bioinformatics--based foldingbased folding

AAGHWWKGPVGEWTLMTYVAVWKHIAAGHWWKGPVGEWTLMTYVAVWKHI

unknown sequenceunknown sequence

Protein Data Bank

big database of known structuresbig database of known structuresatomically detailed representation atomically detailed representation

similar sequences and their structuressimilar sequences and their structures

AAIIGHWWGHWWLRLRGPGPGAGAEWTLEWTLCCTYVAHITYVAHI

LLAGHWAGHWFSFSGGGGVGEWTVGEWTIIMTYMTYAAAAWLVEWLVEHIHI

AGHWWKAGHWWKAAAAVGEVGEYITYEKVADYITYEKVADAVWHIAVWHI

predicted structurepredicted structure

simulated conformational foldingsimulated conformational folding

process guided by atomic energeticsprocess guided by atomic energetics

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Computers can only fold tiny proteins directlyComputers can only fold tiny proteins directly

villin headpiece35 residues

Duan and Kollman 1996 Pande et al. 2006Duan et al. 2007

trp cage miniprotein20 residues

Simmerling et al. 2002Duan et al. 2003

Pitera and Swope 2003Pande et al. 2004

100s-1000s of CPU-years

poly-alanine20 amino acid residues

Pande et al. 2000(movie from folding.stanford.edu)

1GM21GM211 residues11 residues

~10 ns~10 ns

108Y108Y14 residues14 residues

~1 ns~1 ns

1515--ββ15 residues15 residues

~5 ns~5 ns

1E0Q1E0Q17 residues17 residues

~5 ns~5 ns

EK peptideEK peptide14 residues14 residues

~10 ns~10 ns

C peptideC peptide13 residues13 residues

~20 ns~20 ns

Convergence for PDB and literature peptidesConvergence for PDB and literature peptides

~10 ns~10 ns ~1 ns~1 ns ~5 ns~5 ns ~5 ns~5 ns

2JSB2JSB21 residues21 residues

~25 ns~25 ns

1WN81WN822 residues22 residues

~30 ns~30 ns

2JNI2JNI21 residues21 residues

~40 ns~40 ns

nativenative

simulatedsimulated

convergence timeconvergence time

1 ns simulation time 1 ns simulation time

≈≈ 4 CPU days4 CPU days

≈≈ 3.5 hrs real time3.5 hrs real time

~10 ns~10 ns~20 ns~20 ns

2I9M2I9M17 residues17 residues

~65 ns~65 ns

Lin and Shell, J. Comput Chem, 2009.

zipping and assembly

method (ZAM)Shell et al., Biophys. J (2008)

KLAPTGIPPFRLAGTGLPPE

60% identity + 20% similarity

Figure 4-27 Essential Cell Biology (© Garland Science 2010)

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Figure 4-28b Essential Cell Biology (© Garland Science 2010)

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Figure 4-29 Essential Cell Biology (© Garland Science 2010)

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Figure 4-20 Essential Cell Biology (© Garland Science 2010)

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Table 4-1 Essential Cell Biology (© Garland Science 2010)

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Figure 4-30 Essential Cell Biology (© Garland Science 2010)

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zinc ion zinc ion cofactorcofactor

Figure 4-38a Essential Cell Biology (© Garland Science 2010)

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Figure 4-38b Essential Cell Biology (© Garland Science 2010)

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Figure 4-39 Essential Cell Biology (© Garland Science 2010)

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Figure 4-42 Essential Cell Biology (© Garland Science 2010)

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