folding transition and „ foldability ”
DESCRIPTION
Folding transition and „ foldability ”. The phase transition. Density of water: temperature and pressure dependence. The phase diagram of water. H [J/mol]. C v [J/( mol*K )]. Temperature [ o C]. Temperature [ o C]. Vapor. Liquid water. Ice. „Chemical” view. N. U. Two-state model. - PowerPoint PPT PresentationTRANSCRIPT
FOLDING TRANSITION AND „FOLDABILITY”
The phase transition
The phase diagram of water
Density of water: temperature and pressure dependence
Vapor Liquid water Ice
Temperature [oC] Temperature [oC]
„Chemical” view
RT
TG
F
U UF ln
U N Two-state model
I N Three-state modelU
Priovalov and Mathakhadze, Adv. Prot. Chem., 47, 307-425 (1995)
Wild typeAcid-denaturated wild typeL16A mutantC-terminal peptide
Religa et al., J. Mol. Biol., 333, 977-991 (2003)
Millet et al.. Biochemistry 41, 321-325 (2002)
Meersham et al., Biophys. J. 99, 2255–2263 (2010)
Chodankhar et al., PRAMANA Journal of Physics, 71, 1021-1025 (2008)
Staphylococcal protein A, B-domain (46 residues)
UNRES/MREMD simulations
• Berendsen thermostat
• 32 temperatures (250 K T 500 K)
• 4 trajectories/temperature (a total of 128 trajectories)
• 28 million MD steps @t = 4.9 fs
• Last 4 million steps for analysis
• WHAM to compute ensemble averages
Maisuradze et al., J. Am. Chem. Soc. 132, 9444–9452 (2010)
Thermodynamics and ensemble averages
N
C
Experimental structure of 1BDD (red) and most probable conformations (green) at T = 280 K
C rmsd [Å]
Prob
abil
ity
T = 280 K T = 300 K
T = 310 K T = 315 K T = 320 K
T = 325 K T = 350 K
Variation of C rmsd distribution with temperature
Experimental (referemce)
Protein A @ the folding-transition temperature
rmsd=5.3 ÅNative topology
rmsd=9.5 ÅNative topology
rmsd=8.7 Å„mirror image”
topology
rmsd=9.8 Å„mirror image”
topology
Ensemble-averaged contact-probability maps
T=300 K T=325 K (Tf) T=350 K
Experimental (reference)
H-bonding contacts
SC-SC contacts
The folding funnel
Criteria of foldability
1. Gap criterion (Shakhnovich et al., 1994)
2. Large Tf/Tg, (folding to glass-transition temperature) ratio which is the principle of Z-score optimization (Wolynes et al., 1992)
3. Small (Tf-T)/T ratio (T being the hydrophobic collapse temperature; Thirumalai et al., 1996). Inverse proportionality found of the entropy of the excited states to Tf.
4. “Funnel sculpting” (Maritan and Seno, 2003 and Levitt et al., 2003)
5. Hierarchy
Klimov & Thirumalai, Phys. Rev. Lett., 76, 4070-4073 (1996)
f s
level 0 level 1 level 2 native
f – folding time (MFPT to the native structure)
s – residence time
Energy spectra of a lattice model
Liwo et al., J. Phys. Chem. B, 108, 16934-16949 (2004)