Identifying sequence regions undergoing conformational change via predicted continuum secondary structure.
BACKGROUND
Conformational flexibility is essential to the function of many proteins, e.g. catalytic activity. To assist efforts in determining and exploring the functional properties of a protein, it is desirable to automatically identify regions that are prone to undergo conformational changes. It was recently shown that a probabilistic predictor of continuum secondary structure is more accurate than categorical predictors for structurally ambivalent sequence regions, suggesting that such models are suited to characterize protein flexibility.


RESULTS
We develop a computational method for identifying regions that are prone to conformational change directly from the amino acid sequence. The method uses the entropy of the probabilistic output of an 8-class continuum secondary structure predictor. Results for 171 unique amino acid sequences with well-characterized variable structure (identified in the 'Macromolecular movements database') indicate that the method is highly sensitive at identifying flexible protein regions, but false positives remain a problem. The method can be used to explore conformational flexibility of proteins (including hypothetical or synthetic ones) whose structure is yet to be determined experimentally.


BACKGROUND
The predictor, sequence data and supplementary studies are available at http://pprowler.itee.uq.edu.au/sspred/ and are free for academic use.
Bodén
Mikael
M
School of Information Technology and Electrical Engineering, QLD 4072, The University of Queensland Australia. mikael@itee.uq.edu.au
Bailey
Timothy L
TL
D000465:Algorithms; D000595:Amino Acid Sequence; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D013329:Structure-Activity Relationship
D011506:Proteins