Protein Tertiary Structures: Prediction from Amino Acid Sequences

Proteins are polypeptide chains consisting of a large number of amino acid residues that are covalently linked together via amide bonds. The order in which the 20 different amino acids are arranged in a protein chain is also called the primary structure of the protein. The polypeptide backbones of proteins exist in particular conformations known as the secondary structures. The secondary structures as well as their side-chains are then packed into three-dimensional structures referred to as the tertiary structures. The biological function of a protein is often intimately dependent upon its tertiary structure. X-ray crystallography and nuclear magnetic resonance are the two most mature experimental methods used to provide detailed information about protein structures.However, to date the majority of the proteins still do not have experimentally determined structures available. As at December 2000, there were about 14 000 structures available in the protein data bank (PDB, http://www.pdb.org), and there are about 10 106 000 sequence records sequences in GenBank (http://www.ncbi.nlm.nih.gov/Genbank). Thus theoretical methods are very important tools to help biologists obtain protein structure information. The goal of theoretical research is not only to predict the structures of proteins but also to understand howproteinmolecules fold into the native structures. The current methods for protein structure prediction can be roughly divided into three major categories: comparativemodelling; threading; and ab initioprediction. For a given target protein with unknown structure, the general procedure for predicting its structure is described in Figure 1.