Protein Structure Prediction

Abstract The goal of protein structure prediction is to estimate the spatial position of every atom of protein molecules from the amino acid sequence by computational methods. Depending on the availability of homologous templates in the PDB library, structure prediction approaches are categorised into template‐based modelling (TBM) and free modelling (FM). While TBM is by far the only reliable method for high‐resolution structure prediction, challenges in the field include constructing the correct folds without using template structures and refining the template models closer to the native state when templates are available. Nevertheless, the usefulness of various levels of protein structure predictions have been convincingly demonstrated in biological and medical applications. Key Concepts: Evolution is a general principle to guide protein structure and function predictions. Proteins of similar sequence have similar 3D structure. Function of protein is decided by the 3D structure. TBM using homologous templates has the highest accuracy. Template structure can be refined by combining multiple templates. Current physics‐based ab initio folding can only fold small proteins. Threading is an efficient tool for detecting distantly homologous templates. Membrane protein structure prediction is challenging due to the lack of templates. Disordered regions exist in protein which does not possess stable structure but has important function implications.