A Gaussian statistical mechanical model for the equilibrium thermodynamics of barnase folding.
Given an all non-hydrogen-atom potential function that implicitly includes solvation effects, it is possible to adjust its parameters to favor the correct native structure for several proteins over decoys produced by ungapped threading. It is also possible to further train it to reproduce the experimental free energy of unfolding in aqueous solution at 298 K for wild-type barnase and 66 mutants. For this, the native state is represented by the crystal structure at a single energy level with a calculated low degeneracy; the denatured state is represented by the extended conformation and a high calculated degeneracy. The same two-state model can be extended to account for the stability of all 67 sequences toward urea denaturation at 298 K by building in a solvation term that depends on urea concentration. With the addition of one more parameter set to give the correct heat capacity of unfolded barnase in solution, it is possible to approximate the experimental thermodynamics of barnase thermal denaturation: melting temperature, width of thermal transition, deltaG, deltaH, deltaS, and deltaCp. This requires a novel sort of statistical mechanical model where the two states each have a Gaussian density of microscopic state distribution as a function of energy.
Crippen
G M
GM
College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109-1065, USA. gcrippen@umichen.edu
D001407:Bacillus / Q000201:enzymology*; D001426:Bacterial Proteins; D016011:Normal Distribution; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding; D012260:Ribonucleases / Q000737:chemistry* / Q000378:metabolism*; D012997:Solvents; D013696:Temperature; D013816:Thermodynamics; D014508:Urea / Q000494:pharmacology
D001426:Bacterial Proteins; D012997:Solvents; D014508:Urea; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease