A new method for modeling and solving the protein fold recognition problem
Computational recognition of native-like folds from a protein fold database is considered to be a promising alternative approach to the ab initio fold prediction. We present a new and effective method for protein fold recognition through optimally aligning (threading) an amino acid sequence and a protein fold (template). A protein fold, in our database, is represented as a series of core secondary structures, and the alignment quality is determined by three factors. They are (1) the fitness between each amino acid and the environment of its assigned (aligned) template position; (2) pairwise interaction preferences between amino acids that are spatially close; and (3) alignment gap penalties. Our threading algorithm constructs an optimum alignment between an amino acid sequence of size n and a protein fold template of size m in 0((m + n{sup 1+0.5C}-M log(n))n{sup C+1}) time and 0(nm + n{sup C+2}) space, where M is the number of core secondary structures in the fold, and C is a (small) nonnegative integer, determined by a mathematical property of the pairwise interactions in the fold. C is less than or equal to 3 for about 90% of the 296 unique folds in our database, when pairwise interactions are restricted to amino acids < 6{angstrom} apart (measured between their beta carbon atoms). An approximation scheme is developed for fold templates with C > 3, when threading requires too much memory and time to be practical on a typical workstation.
- Research Organization:
- Lockheed Martin Energy Research, Inc., Oak Ridge, TN (United States); Lockheed Martin Energy Systems, Inc., Oak Ridge, TN (United States)
- Sponsoring Organization:
- USDOE, Washington, DC (United States)
- DOE Contract Number:
- AC05-96OR22464; AC05-84OR21400
- OSTI ID:
- 570187
- Report Number(s):
- ORNL/CP-95147; CONF-980313-; ON: DE98001253; TRN: 98:001092
- Resource Relation:
- Conference: 2. annual international conference on computational molecular biology, New York, NY (United States), 22-25 Mar 1998; Other Information: PBD: 1998
- Country of Publication:
- United States
- Language:
- English
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