Abstract

The need for reliable computational methods to determine the biochemical function of these proteins is growing as the determination of protein sequences and structures through genome sequencing and structural genomics efforts grows exponentially. The efforts to address the problem of annotating the function of uncharacterized proteins at the molecular level are reviewed in this paper. The most recent trends in local structure-based methods have received less attention than the sequence- and three-dimensional structure-based methods for protein function prediction. This review focuses primarily on these local structure-based methods. The local spatial arrangements of these residues can be used to identify protein function, and computational methods have been developed to predict the residues that are essential for catalysis. In addition, for proteins with no known function, combining a variety of methods can aid in the acquisition of additional data and the improvement of function predictions. The various methods for predicting the function of proteins with no known function are being evaluated and tested by global initiatives like the Enzyme Function Initiative (EFI), COMputational Bridges to Experiments (COMBREX), and the Critical Assessment of Function Annotation (CAFA). By reducing the number of functional annotations that are either missing or incorrect, these initiatives and global collaborations will add significant value to the existing volume of structural genomics data and improve computational methods for predicting biochemical function [1, 2].