interactions in proteins and their role in structure formation
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Interactions in proteins and their role in structure formation. Levels of protein structure organization. Dominant forces in protein folding. Electrostatic forces Hydrogen bonding and van der Waals interactions Intrinsic properties Hydrophobic forces - PowerPoint PPT PresentationTRANSCRIPT
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INTERACTIONS IN PROTEINS AND THEIR ROLE IN
STRUCTURE FORMATION
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Levels of protein structure organization
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Dominant forces in protein folding
• Electrostatic forces
• Hydrogen bonding and van der Waals interactions
• Intrinsic properties
• Hydrophobic forces
• Conformational entropy (opposes folding)
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Can we say that there are „dominant” forces in protein folding?
Hardly. Proteins are only marginally stable (5 – 20 kBT/molecule). For comparison: water-water H-bond has about 5 kcal/mol (9 kBT/molecule) Consequently, even the tiniest force cannot be ignored.
However, different types of interactions play different roleHydrophobic interaction: compactnessLocal interactions: chain stiffnessHydrogen bonds: architecture
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Local and nonlocal interactions
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Long-range vs. short-range interactions
nij
ij rE
1 n<=3: long range interactions
n>3: short-range interactions
Long-range: electrostatic (charge-charge, charge-dipole, and dipole-dipole) interactions
Short-range: van der Waals repulsion and attraction, hydrophobic interactions
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Electrostatic interactions
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• Lots of like-charges (e.g., side-chain ionization by pH decrease/increase) destabilize protein structure
• Increase of ionic strength destabilizes protein structure
• 5 – 10 kcal/mol / counter-ion (salt-bridge) pair
• A protein contains only a small number of salt bridges, mainly located on the surface (nevertheless, they can be essential).
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Example of a surface salt bridge: salt bridge triad between Asp8, Asp12 and Arg110 on the surface of barnase
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Replacement of charged residues with hydrophobic residues can increase the stability by 3-4 kcal/mol. Example: ARC
repressor
Wild type: salt triad between R31, E36, and R40
Mutant: hydrophobic packing between M31, Y36, and L40
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Potentials of mean force
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Maksimiak et al., J.Phys.Chem. B, 107, 13496-13504 (2003)
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Masunov & Lazaridis, J.Am.Chem.Soc., 125, 1722-1730 (2003)
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Hydrogen-bonding and van der Waals forces
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Aw+Bw
An+Bn
(AB)w
(AB)n
G1=-2.40 kcal/mol
G3=+3.10 kcal/mol
Free energies of N-methylamide dimerization in water (w) and CCl4 (n) solution and transfer between these solvents
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Local interactions are largely determined by Ramachandran map
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Conformations of a terminally-blocked amino-acid residue
C7eq
C7ax
E Zimmerman, Pottle, Nemethy, Scheraga, Macromolecules, 10, 1-9 (1977)
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Energy maps of Ac-Ala-NHMe and Ac-Gly-AHMe obtained with the ECEPP/2 force field
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Energy curve of Ac-Pro-NHMe obtained with the ECEPP/2 force field
L-Pro-68o
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Energy minima of therminally-blocked alanine with the ECEPP/2 force field
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Hydrophobic forces
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Sobolewski et al., J.Phys.Chem., 111, 10765-10744 (2008)
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Dependence of the PMF and cavity contribution to the PMF of two methane molecules on temperature (Sobolewski et al., PEDS, 22, 547-552 (2009)
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S. Miyazawa & R.L. Jernigan, R. L. 1985. Estimation of effective interresidue contact energies from protein crystal structures: quasi-chemical approximation. Macromolecules, 18:534-552, 1985.
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C M F I L V W Y A G T S Q N E D H R K P
P
K
R
H
D
E
N
Q
S
T
G
A
Y
W
V
L
I
F
M
C
Color map of the MJ table
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Conformational entropy