Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and Bayesian scoring functions

TitleAssembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and Bayesian scoring functions
Publication TypeJournal Article
Year of Publication1997
AuthorsSimons, K. T., Kooperberg C., Huang E., & Baker D.
JournalJournal of molecular biology
Volume268
Issue1
Pagination209-25
Date Published1997 Apr 25
ISSN0022-2836
KeywordsBayes Theorem, Computer Simulation, Databases, Factual, Models, Molecular, Models, Statistical, Peptide Fragments, Primary Publication, Protein Folding, Protein Structure, Tertiary, Proteins, Sequence Homology, Amino Acid
Abstract

We explore the ability of a simple simulated annealing procedure to assemble native-like structures from fragments of unrelated protein structures with similar local sequences using Bayesian scoring functions. Environment and residue pair specific contributions to the scoring functions appear as the first two terms in a series expansion for the residue probability distributions in the protein database; the decoupling of the distance and environment dependencies of the distributions resolves the major problems with current database-derived scoring functions noted by Thomas and Dill. The simulated annealing procedure rapidly and frequently generates native-like structures for small helical proteins and better than random structures for small beta sheet containing proteins. Most of the simulated structures have native-like solvent accessibility and secondary structure patterns, and thus ensembles of these structures provide a particularly challenging set of decoys for evaluating scoring functions. We investigate the effects of multiple sequence information and different types of conformational constraints on the overall performance of the method, and the ability of a variety of recently developed scoring functions to recognize the native-like conformations in the ensembles of simulated structures.

Alternate JournalJ. Mol. Biol.
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