Optimizing potentials for the inverse protein folding problem

被引:23
作者
Chiu, TL
Goldstein, RA [1 ]
机构
[1] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Div Biophys Res, Ann Arbor, MI 48109 USA
来源
PROTEIN ENGINEERING | 1998年 / 11卷 / 09期
关键词
contact potential; lattice proteins; sequence recognition; structure recognition; protein folding;
D O I
10.1093/protein/11.9.749
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
Inverse protein folding, which seeks to identify sequences that fold into a given structure, has been approached by threading candidate sequences onto the structure and scoring them with database-derived potentials. The sequences with the lowest energies are predicted to fold into that structure. It has been argued that the limited success of this type of approach is not due to the discrepancy between the scoring potential and the true potential but is rather due to the fact that sequences choose their lowest-energy structure rather than structures choosing the lowest-energy sequences. Here we develop a non-physical potential scheme optimized for the inverse folding problem. We maximize the average probability of success for a set of lattice proteins to obtain the optimal potential energy function, and show that the potential obtained by our method is more likely to produce successful predictions than the true potential.
引用
收藏
页码:749 / 752
页数:4
相关论文
共 23 条
[1]   PRINCIPLES THAT GOVERN FOLDING OF PROTEIN CHAINS [J].
ANFINSEN, CB .
SCIENCE, 1973, 181 (4096) :223-230
[2]   A METHOD TO IDENTIFY PROTEIN SEQUENCES THAT FOLD INTO A KNOWN 3-DIMENSIONAL STRUCTURE [J].
BOWIE, JU ;
LUTHY, R ;
EISENBERG, D .
SCIENCE, 1991, 253 (5016) :164-170
[3]   Optimizing energy potentials for success in protein tertiary structure prediction [J].
Chiu, TL ;
Goldstein, RA .
FOLDING & DESIGN, 1998, 3 (03) :223-228
[4]   PREDICTION OF PROTEIN FOLDING FROM AMINO-ACID-SEQUENCE OVER DISCRETE CONFORMATION SPACES [J].
CRIPPEN, GM .
BIOCHEMISTRY, 1991, 30 (17) :4232-4237
[5]  
Crippen GM, 1996, PROTEINS, V26, P167
[6]  
CRIPPEN GM, 1995, PROTEIN FOLDS DISTAN, P189
[7]   SIMILAR AMINO-ACID-SEQUENCES - CHANCE OR COMMON ANCESTRY [J].
DOOLITTLE, RF .
SCIENCE, 1981, 214 (4517) :149-159
[8]  
GILL PE, 1974, NUMREICAL METHODS CO
[9]   IN SEARCH OF THE IDEAL PROTEIN-SEQUENCE [J].
GODZIK, A .
PROTEIN ENGINEERING, 1995, 8 (05) :409-416
[10]   PROTEIN TERTIARY STRUCTURE RECOGNITION USING OPTIMIZED HAMILTONIANS WITH LOCAL INTERACTIONS [J].
GOLDSTEIN, RA ;
LUTHEYSCHULTEN, ZA ;
WOLYNES, PG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (19) :9029-9033