Theoretical estimations of changes in side chain configurational entropy are essential for understanding the different contributions to the overall thermodynamic behavior in folding and binding. The configurational entropy of any given side chain in any particular protein can be evaluated from the complete energy profile of the side chain. The energy profiles can be calculated using the side chain single bond dihedrals as the only independent variables as long as the structures at each value of the dihedrals are allowed to relax through small changes in valence bond angles. The probabilities of side chain conformers obtained from these energy profiles are very similar to the conformer populations obtained from side chain preferences in the Protein Data Bank. Also, side chain conformational entropies obtained from the energy profiles agree well with those obtained from the conformer populations. Changes in side chain configurational entropy can be computed as differences in conformational entropy because, in most cases, the frequency of the rotational oscillation around the energy minimum of any given conformer does not appear to change significantly in the reaction. The calculated changes of side chain conformational entropy were compared with experimental values. The only available experimental data - the effect of side chain substitution on the stability of a helixes - were used for this comparison. The experimental values were corrected to subtract the solvent contributions. This comparison yields an excellent agreement between calculated and experimental values, validating not only the theoretical estimates but also the separability of the entropic contributions into configurational terms and solvation related terms.
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