Modeling the Interaction of Trehalose-6-Phosphate Synthase and UDP-Glucose Bycomputational Methods

Background: Trehalose, an integral component of the cell-wall glycolipids of Mycobacteriumis an unusual nonreducing disaccharide, which plays a variety of biological roles from food storage to cellular protection under diverse environmental stresses (e.g. high pressure, heat-shock, reactive oxygen species, free radicals etc.). Primary enzymatic route to trehalose first involves the transfer of glucose from an UDP-glucose donor to glucose-6-phosphate to form alpha, alpha-1 and 1 trehalose-6-phosphate. It serves as a stress protectant in a range of organisms especially in resurrection of plants and many microorganisms. In addition, the principal role of trehalose is as an important metabolite due to its unique properties like high hydrophobicity, chemical stability, non-hygroscopic glass formation and no internal hydrogen bond formation is worthy to mention.

Methods: MODELLER, a command-line bioinformatics tools and various other bioinformatics programmes and servers like RAMPAGE, PRO-CHECK, Dallite, Errat, Verify 3D were used for analysis and validation of final structures created through homology modeling.

Results: The present work was done for virtual screening of the enzyme Trehalose-6-Phosphate Synthase and studying the interaction with ligand UDP. The crystal structure of TPS-UDP glucose was used for studying the proteinligand interaction. Further homology modeling of the protein was done in detail by deploying basic operation of Argus Lab; Chimer graphics interface to display and manipulate modeled protein.

Application: We report here virtual screening of the enzyme Trehalose-6-Phosphate Synthase to unzip protein-ligand interaction through homology search or comparative modeling to pinpoint potential of the modeled/created protein and to analyze and validate the final structures using various informatics tools.