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Physical interactions that determine the properties

of proteins

Petsko-Ringe 1.0 to 1-9Proteins. Creighton 4

The biological activities of proteins

Unique environments and orientations of the functional groups

Interactions with the environment:

WaterSaltsMembranesOther proteinsNucleic Acids

Noncovalent interactions

2

Noncovalent interactions

• Short range• Ionic • Hydrogen bonds• van der Waals

Short range repulsions

3

Electrostatic forces

• strength depends on the distance of the charges and what occupies the space between the charges

+ - + -non-polarsubstanceor vacuum

polar, e.g.water

strong attraction weak attraction

Dielectric Constants and Permanent Molecular Dipole Moments

of Some Common Solvents

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Figure 8-57 Dipole-dipole interactions.

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Hydrogen bonding

• requires one donor and one acceptor• bonds are directional (distance and angle

between donor and acceptor are important)

\C=O/

Preferred area for accepting H-bondsD-H |A

donor acceptor

Donor, hydrogen and acceptor atomare arranged along a straight line

Hydrogen atom is located near thelone pair electrons of the acceptor

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Hydrogen bonds (~1.9-2 Ǻ)• N-H O=• O-H -O-• S-H -N=• C-H -S-

• -S-• π electrons

Solubilities:

Relative hydrophilicities

of amino acids side chains

Biochemistry 198120, 849-55

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Interactions between molecules in water

• A + B ↔ AB Kassoc=[AB]/([A].[B])

• Interactions between individual molecules in solution are very weak

Kassoc~0.02 M-1

Debye-Hückel screening

• Deff = Dwater . exp(+κd)

• Dwater decrease at higher temperatures

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Figure 8-58 The orientational preference of water molecules next to a nonpolar solute.

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•H2O forms an ordered clathrate cage around non-polar substances.

•This is energetically unfavorable because of the high negative ΔS.

Interaction of water with non-polar substances

The hydrophobic effect

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What drives protein folding?

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© 2004 New Science Press Ltd new-science-press.com

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© 2004 New Science Press Ltd new-science-press.com

pKa values of the ionizable groupsof proteins (Prot. Sci. 2006 15,1-5)

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© 2004 New Science Press Ltd new-science-press.com

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NSP In association withBioMed Central

Proteins: Inside and outside

Slice through a globular protein

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23 1: Hydrophobic core

2: Protein surface3: Water (solvent)