Design of an optimal Chebyshev-expanded discrimination function for globular proteins

被引:19
作者
Fain, B [1 ]
Xia, Y [1 ]
Levitt, M [1 ]
机构
[1] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA
关键词
proteins; energy functions; optimization; Chebyshev;
D O I
10.1110/ps.0200702
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We describe the construction of a scoring function designed to model the free energy of protein folding. An optimization technique is used to determine the best functional forms of the hydrophobic, residue-residue and hydrogen-bonding components of the potential. The scoring function is expanded by use of Chebyshev polynomials, the coefficients of which are determined by minimizing the score, in units of standard deviation, of native structures in the ensembles of alternate decoy conformations. The derived effective potential is then tested on decoy sets used conventionally in such studies. Using our scoring function, we achieve a high level of discrimination between correct and incorrect folds. In addition, our method is able to represent functions of arbitrary shape with fewer parameters than the usual histogram potentials of similar resolution. Finally, our representation can be combined easily with many optimization methods, because the total energy is a linear function of the parameters. Our results show that the techniques of Z-score optimization and Chebyshev expansion work well.
引用
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页码:2010 / 2021
页数:12
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