Side-chain conformational entropy in protein unfolded states.
The largest force disfavoring the folding of a protein is the loss of conformational entropy. A large contribution to this entropy loss is due to the side-chains, which are restricted, although not immobilized, in the folded protein. In order to accurately estimate the loss of side-chain conformational entropy that occurs upon folding it is necessary to have accurate estimates of the amount of entropy possessed by side-chains in the ensemble of unfolded states. A new scale of side-chain conformational entropies is presented here. This scale was derived from Monte Carlo computer simulations of small peptide models. It is demonstrated that the entropies are independent of host peptide length. This new scale has the advantage over previous scales of being more precise with low standard errors. Better estimates are obtained for long (e.g., Arg and Lys) and rare (e.g., Trp and Met) side-chains. Excellent agreement with previous side-chain entropy scales is achieved, indicating that further advancements in accuracy are likely to be small at best. Strikingly, longer side-chains are found to possess a smaller fraction of the theoretical maximum entropy available than short side-chains. This indicates that rotations about torsions after chi(2) are significantly affected by side-chain interactions with the polypeptide backbone. This finding invalidates previous assumptions about side-chain-backbone interactions. Proteins 2000;40:443-450.
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Center for Structural Biology, Department of Biochemistry, University of Kentucky, Lexington, Kentucky 40536-0298, USA. trvor@euripides.gws.uky.edu
D000596:Amino Acids / Q000737:chemistry*; D003198:Computer Simulation; D019277:Entropy; D008962:Models, Theoretical; D009010:Monte Carlo Method; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D015203:Reproducibility of Results
D000596:Amino Acids