Determination of optimal Chebyshev-expanded hydrophobic discrimination function for globular proteins

We describe the development of a scoring function designed to model the hyd rophobic effect in protein folding. An optimization technique is used to de termine the best functional form of the hydrophobic potential. The scoring function is expanded using the Chebyshev polynomials, for which the coeffic ients are determined by minimizing the Z-score of native structures in the ensembles of alternate conformations. (The Z-score is the score relative to the mean, measured in units of standard deviation.) The derived effective potential is tested on decoy sets conventionally used in such studies. The function is able to discriminate very well between correct and incorrect fo lds, despite the fact that it simply counts the number of neighbors of each amino acid. Our results show that the techniques of Z-score optimization a nd Chebyshev expansion work, and work well. Our results also confirm that h ydrophobic effect is one of the principal driving forces in protein folding .