The function of a hypothetical protein can be predicted by domain homology searches with various confidence levels[2]. Conserved domains are available in the hypothetical proteins which need to be compared with the known family domains by which hypothetical protein could be classified into particular protein families even though they have not been in vivo investigated. The function of hypothetical protein could also be predicted by homology modelling, in which hypothetical protein has to align with known protein sequence whose three dimensional structure is known and by modelling method if structure predicted then the capability of hypothetical protein to function could be ascertained computationally[2][3].Further, approaches to annotate function to hypothetical proteins include determination of 3-dimensional structure of these proteins by structural genomics initiatives, understanding the nature and mode of prosthetic group/metal ion binding, fold similarity with other proteins of known functions and annotating possible catalytic site and regulatory site.[4] Structure prediction with biochemical function assessment by screening for various substrate is another promising approach to annotate function[2]