Ab Initio Protein Structure Prediction

Predicting protein 3D structures from the amino acid sequence still remains as an unsolved problem after five decades of efforts. If the target protein has a homologue already solved, the task is relatively easy and high-resolution models can be built by copying the framework of the solved structure. However, such a modelling procedure does not help answer the question of how and why a protein adopts its specific structure. If structure homologues (occasionally analogues) do not exist, or exist but cannot be identified, models have to be constructed from scratch. This procedure, called ab initio modelling, is essential for a complete solution to the protein structure prediction problem; it can also help us understand the physicochemical principle of how proteins fold in nature. Currently, the accuracy of ab initio modelling is low and the success is limited to small proteins (<100 residues). In this chapter, we give a review on the field of ab initio modelling. Focus will be put on three key factors of the modelling algorithms: energy function, conformational search, and model selection. Progresses and advances of a variety of algorithms will be discussed.