Energy landscape guiding conformational search to the native state
The energy landscape funnel (Wolynes, Onuchic, Dill ~1992) explains how proteins avoid Levinthal's paradox: rather than random search through 10^300 conformations, a funnel-shaped landscape channels folding. Conformational entropy S decreases as the chain converges on native contacts, while energy E decreases faster, giving a net decrease in free energy F=E−TS.