Protein Folding Energy Landscape

Funnel Theory · Levinthal Paradox · HP Lattice Model · Chaperones

Landscape Parameters

6
3
0.5

HP Lattice Model

H=hydrophobic (black), P=polar (white)
E = −1 for each H-H contact (non-bonded)
Minimize: maximize buried H residues
Energy: 0
H-H contacts: 0

Folding Dynamics

Levinthal Paradox: if a 100-residue protein
sampled all 3¹⁰⁰ ≈ 5×10⁴⁷ conformations,
it would take longer than the universe's age.
Yet proteins fold in microseconds to seconds!
Solution: the energy landscape is a funnel.
Native state is an attractor — no random search.