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.
The process of annotating the function of hypothetical proteins involves using various techniques like structural genomics projects to determine their 3D structure, analyzing how they bind prosthetic groups or metal ions, comparing their folds to those of known functional proteins, and identifying potential catalytic and regulatory regions within them.