figure 4-1 essential cell biology (© garland science 2010)shell/che170/proteins-slides.pdf ·...
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Figure 4-1 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
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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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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
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Figure 4-6 Essential Cell Biology (© Garland Science 2010)
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native state
(unfolded)
aggregates
(insoluble)
unfolded protein
misfolded state
(solvent-exposed
hydrophobic groups) proteolytic
degradation
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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)
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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.
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zipping and assembly
method (ZAM)Shell et al., Biophys. J (2008)
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KLAPTGIPPFRLAGTGLPPE
60% identity + 20% similarity
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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
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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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