| 摘要 |
This invention provides methods for computationally determining protein structure by employing combined threading to optimize threading results, Sequence profiles are employed to generate an initial probe-template alignment that is then used in the evaluation of pair interactions. Two types of sequence profiles are employed, a "close" set, typically comprised of sequences whose identity lies between about 35 % and about 90 %; and a "distant" set, typically comprised of sequences with a FASTA E-score less than 10. preferably, a total of four scoring functions are used in a hierarachical process to provide an initial alignment of the probe sequence in each of the templates. The same database is then screened with a scoring function comprised of sequence plus secondary structure, and further preferably includes pair interaction profiles. In preferred embodiments, a set of the top scoring sequences (for example, four scoring functions times the top five structures) is used to construct a protein-specific pair potential based on consensus side chain contacts occurring in 25 % of the structures. In subsequent threading iterations, the protein-specific pair potential, when combined in a composite fashion, is found to be more sensitive in identifying the correct pairs than when th eoriginal statistical potential is used, and it increases the number of recognized structures for the combined scoring functions. |
