An Introduction to Protein Contact Prediction

A fundamental problem in molecular biology is the prediction of the three-dimensional structure of a protein from its amino acid sequence. However, molecular modeling to find the structure is at present intractable and is likely to remain so for some time, hence intermediate steps such as predicting which residues pairs are in contact have been developed. Predicted contact pairs have been used for fold prediction, as an initial condition or constraint for molecular modeling, and as a filter to rank multiple models arising from homology modeling. As contact prediction has advanced it is becoming more common for 3D structure predictors to integrate contact prediction into structure building, as this often gives information that is orthogonal to that produced by other methods. This chapter shows how evolutionary information contained in protein sequences and multiple sequence alignments can be used to predict protein structure, and the state-of-the-art predictors and their methodologies are reviewed.