S. Govindarajan et Ra. Goldstein, ON THE THERMODYNAMIC HYPOTHESIS OF PROTEIN-FOLDING, Proceedings of the National Academy of Sciences of the United Statesof America, 95(10), 1998, pp. 5545-5549
The validity of the thermodynamic hypothesis of protein folding was ex
plored by simulating the evolution of protein sequences. Simple models
of lattice proteins were allowed to evolve by random point mutations
subject to the constraint that they fold into a predetermined native s
tructure with a Monte Carlo folding algorithm. We employed a simple an
alytical approach to compute the probability of violation of the therm
odynamic hypothesis as a function of the size of the protein, the frac
tion of the total number of possible conformations which are kinetical
ly accessible, and the roughness of the free-energy landscape. It was
found that even if the folding is under kinetic control, the sequence
will evolve so that the native state is most often the state of minimu
m free energy.