Sisyphus and prediction of protein structure

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), 2 0 and I D prediction have reopened the field. Mean-forcepotentials derived from the protein databases can distinguish between correct and incorrect models (30). Inter-residue contacts (2D) can be detected by analysis of correlated mutations, albeit with low accuracy. Secondary structure, solvent accessibility and transmembrane helices (I D) can be predicted with signicantly 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 injuencing experiments in molecular biology.