Clustering of low-energy conformations near the native structures of small proteins

TitleClustering of low-energy conformations near the native structures of small proteins
Publication TypeJournal Article
Year of Publication1998
AuthorsShortle, D., Simons K. T., & Baker D.
JournalProceedings of the National Academy of Sciences of the United States of America
Date Published1998 Sep 15
KeywordsComputer Simulation, Primary Publication, Protein Conformation, Protein Denaturation, Protein Folding, Proteins

Recent experimental studies of the denatured state and theoretical analyses of the folding landscape suggest that there are a large multiplicity of low-energy, partially folded conformations near the native state. In this report, we describe a strategy for predicting protein structure based on the working hypothesis that there are a greater number of low-energy conformations surrounding the correct fold than there are surrounding low-energy incorrect folds. To test this idea, 12 ensembles of 500 to 1,000 low-energy structures for 10 small proteins were analyzed by calculating the rms deviation of the Calpha coordinates between each conformation and every other conformation in the ensemble. In all 12 cases, the conformation with the greatest number of conformations within 4-A rms deviation was closer to the native structure than were the majority of conformations in the ensemble, and in most cases it was among the closest 1 to 5%. These results suggest that, to fold efficiently and retain robustness to changes in amino acid sequence, proteins may have evolved a native structure situated within a broad basin of low-energy conformations, a feature which could facilitate the prediction of protein structure at low resolution.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
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