Sisyphus and prediction of protein structure

TitleSisyphus and prediction of protein structure
Publication TypeJournal Article
Year of Publication1997
AuthorsRost, B, O'Donoghue, S
JournalComput Appl Biosci
KeywordsAmino Acid, Chemical Molecular Structure Mythology Protein Folding Protein Structure, Computers Databases, Factual Models, Secondary Proteins/*chemistry/genetics Sequence Alignment/methods/statistics & numerical data Sequence Homology

The problem of predicting protein structure from the sequence remains fundamentally unsolved despite more than three decades of intensive research effort. However, new and promising methods in three-dimensional (3D), 2D and 1D prediction have reopened the field. Mean-force-potentials derived from the protein databases can distinguish between correct and incorrect models (3D). Inter-residue contacts (2D) can be detected by analysis of correlated mutations, albeit with low accuracy. Secondary structure, solvent accessibility and transmembrane helices (1D) can be predicted with significantly improved accuracy using multiple sequence alignments. Some of these new prediction methods have proven accurate and reliable enough to be useful in genome analysis, and in experimental structure determination. Moreover, the new generation of theoretical methods is increasingly influencing experiments in molecular biology.