Protein structure prediction: recognition of primary, secondary, and tertiary structural features from amino acid sequence

Abstract

This review attempts a critical stock-taking of the current state of the science aimed at predicting structural features of proteins from their amino acid sequences. At the primary structure level, methods are considered for detection of remotely related sequences and for recognizing amino acid patterns to predict posttranslational modifications and binding sites. The techniques involving secondary structural features include prediction of secondary structure, membrane-spanning regions, and secondary structural class. At the tertiary structural level, methods for threading a sequence into a mainchain fold, homology modeling and assigning sequences to protein families with similar folds are discussed. A literature analysis suggests that, to date, threading techniques are not able to show their superiority over sequence pattern recognition methods. Recent progress in the state of ab initio structure calculation is reviewed in detail. The analysis shows that many structural features can be predicted from the amino acid sequence much better than just a few years ago and with attendant utility in experimental research. Best prediction can be achieved for new protein sequences that can be assigned to well-studied protein families. For single sequences without homologues, the folding problem has not yet been solved.