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Polymer principles and protein folding

Published online by Cambridge University Press:  01 June 1999

KEN A. DILL
Affiliation:
University of California, San Francisco, 3333 California Street, Ste. 415, San Francisco, California 94118
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Abstract

This paper surveys the emerging role of statistical mechanics and polymer theory in protein folding. In the polymer perspective, the folding code is more a solvation code than a code of local φψ propensities. The polymer perspective resolves two classic puzzles: (1) the Blind Watchmaker's Paradox that biological proteins could not have originated from random sequences, and (2) Levinthal's Paradox that the folded state of a protein cannot be found by random search. Both paradoxes are traditionally framed in terms of random unguided searches through vast spaces, and vastness is equated with impossibility. But both processes are partly guided. The searches are more akin to balls rolling down funnels than balls rolling aimlessly on flat surfaces. In both cases, the vastness of the search is largely irrelevant to the search time and success. These ideas are captured by energy and fitness landscapes. Energy landscapes give a language for bridging between microscopics and macroscopics, for relating folding kinetics to equilibrium fluctuations, and for developing new and faster computational search strategies.

Type
REVIEWS
Copyright
© 1999 The Protein Society

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