Protein Folding

How do proteins adopt functional native fold

noncovalent bonds dictate protein structure

Detergent

bind to exposed hydrophobic regions and disrupt hydrophobic packing

Chaotropic Agents

weaken hydrophobic effect and h bonding

Reducing agent

break covalent bonds

Urea

chaotropic agent that denatures proteins and weakens & h bonding

Beta-Mercaptoethanol

reducing agent that destabilizes disulfide-stabilized tertiary structure

Anfinsen’s Experiment

Proved that amino acid sequence contains the folding information

Levinthal’s paradox

Protein conformation is not random but directed. if a protein had a 100 aa and each aa had 10 confirmations then it would take 10^100 picoseconds too long

Process of Protein folding

in 1ms: unfolded → secondary structure by H bonding
Secondary → molten globule by hydrophobic collapse (nonpolar sides hide)
molten → to native state is driven by h bonding, LDFs, and ionic interactions

Molten globules

Partially folded conformations of proteins