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 pi 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.