Exploring structures in protein folding funnels with free energy functionals: the denatured ensemble.
We discuss the formulation of free energy functionals that describe the formation of structure in partially folded proteins. These free energy functionals take into account the inhomogeneous nature of contact energies, chain entropy and cooperative contributions reflecting the many body character of some folding forces like hydrophobicity, but do not directly account for non-native contacts because they assume the validity of the minimal frustration principle. We show how the free energy functionals can be used to interpret experiments on partially folded proteins that probe the fractional occupancy of specific local structures. In particular, we study the hydrogen protection factors in lysozyme studied in transient experiments by Gladwin and Evans and by Nash and Jonas using equilibrium pressure denaturation and the NMR order parameters measured by Dobson and Kim for the homologous protein alpha-lactalbumin.
Shoemaker
B A
BA
School of Chemical Sciences, University of Illinois, Urbana, IL, 61801, USA.
Wolynes
P G
PG
D000818:Animals; D002645:Chickens; D007768:Lactalbumin / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
D007768:Lactalbumin; D009113:Muramidase