TY - JOUR
T1 - Clustering of low-energy conformations near the native structures of small proteins
AU - Shortle, D.
AU - Simons, K. T.
AU - Baker, D.
PY - 1998/9/15
Y1 - 1998/9/15
N2 - 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 Cα 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-Å 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.
AB - 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 Cα 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-Å 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.
UR - http://www.scopus.com/inward/record.url?scp=0032530578&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032530578&partnerID=8YFLogxK
U2 - 10.1073/pnas.95.19.11158
DO - 10.1073/pnas.95.19.11158
M3 - Article
C2 - 9736706
AN - SCOPUS:0032530578
SN - 0027-8424
VL - 95
SP - 11158
EP - 11162
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 19
ER -