PROTEIN PHYSICS

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PROTEIN PHYSICS

• A. V. Finkelstein
• O. B. Ptitsyn
• LECTURE 3
• www.nd.edu/aasztalo

Andrea Asztalos, 2007 May 4
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QUESTIONS

• Amino Acid Synthesis
• What a protein can and can not do? Flexibility,
  hybridization,
• Chemical bonds in a protein
• How does an alpha-helix end and start?
• The energetic scale of different interactions
• When does a protein die? What is its lifetime?
• How does a domain start and end?
• Ramachandran Plot
• How can you destroy a peptide bond? Whats the
  strength of a peptide bond?

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CHEMICAL BONDS - Strength

• Covalent Bond 50 - 100kcal/mol
• Ionic Bond 5 - 80kcal/mol
• Hydrogen Bond 3 - 6kcal/mol
• Hydrophobic Interaction 0.5 - 3kcal/mol (not a
  bond per se)
• Van der Waals Interaction 1kcal/mol

Van der Waals int. lt Hydrogen Bond lt Ionic Bond
lt Polar Covalent Bond lt Non-polar Covalent Bond
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COVALENT BOND
Single Covalent Bond - two atoms share a pair of
electrons
H H gt H2
Non-polar CB the bonding electron pair is
equally shared between the two atoms
Polar CB the bonding electron pair is shared
unequally between the two atoms
Non-polar CB
Polar CB
Ionic Bond
H H
H d F d-
Na - Cl-
ELECTRONEGATIVITY (Linus Pauling)

• ability of an atom in a CB to attract shared
  electrons to itself

Double Covalent Bond two shared pairs of
electrons join the same pair of atoms Triple
Covalent Bond three shared pairs of electrons
join the same pair of atoms
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COVALENT BOND
DOUBLE Covalent Bond
RESPONSIBLE
Free rotation around the single bond Not free
rotation around the double bond
FOR
A double bond is stronger than a single bond but
not twice as strong!!!!
O
.
.
.
.
.
.
.
.
O
O
schematically
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BONDING in a PROTEIN
C
ENERGIES
C H 99.3 kcal/mol C N 68 kcal/mol C
C 82 kcal/mol C C 142 kcal/mol C N
147 kcal/mol C O 165 kcal/mol C O 80
kcal/mol H N 93.3 kcal/mol S H 82
kcal/mol H H 104kcal/mol
C(alpha) is sp3 hybridized gt tetrahedral
structure
C, N sp2 hybridized atoms
C N peptide bond, double bond gt rigid,
planar structure
Delocalized electron cloud covering the three
atoms
Remark Lone pairs as well as bonding electron
pairs can occupy hybrid orbitals
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FLEXIBILITY
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DIHEDRAL ANGLES
CIS
0
180
TRANS
60, 180, 300
Minimum Rotational Energy at
0
60
0, 120, 240
Maximum Rotational Energy at
30, 90, 150, 210, 270, 330
Minimum Rotational Energy at
30
0, 60, 120, 180, 240, 300
Maximum Rotational Energy at
0
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Van der Waals INTERACTIONS
RESPONSIBLE FOR cis trans configurations,
restrictions on backbone torsional angles
Formed between any two molecules
Two main Contributions

• Strong repulsion at short distances

saturated orbital clouds repel each other

• Weak attraction at distances just greater than
  the sum
• of the atomic radii

induced dipole-dipole interaction
The functional form most often used to describe
VdW interactions is the Lennard - Jones potential
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Van der Waals INTERACTIONS
E0 the minimum energy
R0 distance at which the energy is minimum
Rmin minimum distance existing in the
crystalline state
RvdW van der Waals radius
Typical parameters of van der Waals interaction
potentials
Note The values in red are from a different
reference
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CONSEQUENCES
a).
TRANS
CIS
2.8 Å lt Rmin 3.0 Å for C C interaction
b).
Restrictions on backbone torsional angles
Rmin(C C) 3 Å
Rmin(N N) 2.7Å
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What a RESIDUE can do?
RAMACHANDRAN PLOT
Preferred region outlined in orange Disfavored
but allowed region outlined in gold
SPECIAL CASES
Glycine
Proline
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Ramachandran Plots
Proline
Glycine
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Important folding factors

• Polar side chains tend to be on the surface in
  contact with water
• Nonpolar side chains tend to be internal
• Very hydrophobic side chains tend to cluster
• H-bonds form between the carbonyl in I peptide
  bond and the H attached to a N in 2 peptide bond
• The presence of S-S disulfide bonds
• Polar with polar side chains and respectively
  nonpolar with nonpolar side chains never get too
  close to each other
• H-bonds are easily formed
• Ionic bonds between oppositely charged groups in
  acidic and basic amino acids.