Guessing Protein Structures

The protein folding problem has now stood for over 30 years. The coding of protein structure by the amino acid sequence was first proposed by Anfinsen and colleagues in 1961. The first attempts to predict protein structure from sequence were made in the late 1960's following the solution of the first few three dimensional structures of proteins by X-ray crystallography.

The first notable successes in prediction came with the work of Chou and Gerald Fasman and of Barry Robson and colleagues (known as GOR). These programs were capable of predicting if each amino acid was part of a helix, a sheet or a coil region in a protein. It Chou and Fasman's method worked for around 52% of amino acids. The GOR method was correct for 54% of amino acids. These programs worked using statistics gathered on existing protein structures in the case of the GOR method and on simple rules developed from observation of structures in the case of Chou and Fasman's method. The methods were applied to single sequences.

One would expect a method which randomly assigned amino acids to structures to achieve only 33% accuracy, so these methods were at least doing a lot better than chance. In fact the random chance level is a little higher, at around 40%, due to the proportions of strand, helix and coil present in most proteins.