On the polymer physics origins of protein folding thermodynamics.
A remarkable feature of the spontaneous folding of many small proteins is the striking similarity in the thermodynamics of the folding process. This process is characterized by simple two-state thermodynamics with large and compensating changes in entropy and enthalpy and a funnel-like free energy landscape with a free-energy barrier that varies linearly with temperature. One might attribute the commonality of this two-state folding behavior to features particular to these proteins (e.g., chain length, hydrophobic/hydrophilic balance, attributes of the native state) or one might suspect that this similarity in behavior has a more general polymer-physics origin. Here we show that this behavior is also typical for flexible homopolymer chains with sufficiently short range interactions. Two-state behavior arises from the presence of a low entropy ground (folded) state separated from a set of high entropy disordered (unfolded) states by a free energy barrier. This homopolymer model exhibits a funneled free energy landscape that reveals a complex underlying dynamics involving competition between folding and non-folding pathways. Despite the presence of multiple pathways, this simple physics model gives the robust result of two-state thermodynamics for both the cases of folding from a basin of expanded coil states and from a basin of compact globule states.
Department of Physics, Hiram College, Hiram, Ohio 44234, USA.
Mark P
MP
Taylor
Institut für Physik, Martin-Luther-Universität, D-06099 Halle (Saale), Germany.
Wolfgang
W
Paul
Institut für Physik, Johannes-Gutenberg-Universität, Staudinger Weg 7, D-55099 Mainz, Germany.
Kurt
K
Binder
D008958:Models, Molecular; D011108:Polymers / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D013696:Temperature
D011108:Polymers