Protein side-chain conformational entropy derived from fusion data--comparison with other empirical scales.
The loss of conformational entropy of protein side-chains is a major effect in the energetics of folding. The simplest approach is to enumerate the number of freely rotatable bonds. Recently, two scales of side-chain conformational entropy have been proposed based on the definition of entropy as the Boltzmann sampling over all accessible states (S = -R sigma p(i)lnp(i), where p(i) is the probability of being in a rotameric state). In one scale, derived only for aliphatic and aromatic side-chains, the values of p(i) were obtained from Monte Carlo simulations. In the other scale, the observed frequencies of different rotameric states in a database of protein crystal structures yielded an estimate for p(i). Here an empirical estimation of the fusion entropy of the side-chains is used to derive a third scale. The fusion entropy is obtained as a sum of empirically derived contributions from component hydrocarbon and functional groups. There is a good agreement between the fusion scale and the other two scales. This suggests that the magnitude of conformational entropy is being correctly established.
Sternberg
M J
MJ
Biomolecular Modelling Laboratory, Imperial Cancer Research Fund, London, UK.
Chickos
J S
JS
D003198:Computer Simulation; D008958:Models, Molecular; D009010:Monte Carlo Method; D011487:Protein Conformation; D017510:Protein Folding; D013816:Thermodynamics