Prediction of protein structure from sequence.
Methods to predict the three-dimensional structure of a protein from its sequence are reviewed. The approaches to derive information about the local conformation from the local sequence include hydrophobicity plots, secondary structure prediction and the identification of short, functional sequence motifs. The most reliable method of tertiary structure prediction is model building from the experimentally determined coordinates of a protein with an homologous sequence. This approach is illustrated by a prediction of the three-dimensional structure of human cytochrome P450-IA1. If no known homologous structure is available, then the only approach is to suggest models for the tertiary fold of proteins by packing together predicted secondary structures. A three-dimensional model for the dimerisation of the transmembrane alpha-helices of neu, a tyrosine kinase growth factor receptor, is described. In general, structure prediction can suggest approaches for regulating protein activity that may lead to new pharmaceutical therapies for cancer.
Sternberg
M J
MJ
Biomolecular Modelling Laboratory, Imperial Cancer Research Fund, London, U.K.
Zvelebil
M J
MJ
D000595:Amino Acid Sequence; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D066246:ErbB Receptors / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases; D013329:Structure-Activity Relationship
D003577:Cytochrome P-450 Enzyme System; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C064740:epidermal growth factor receptor-neu receptor