Computational modeling and evaluation of best potential drug targets through comparative modeling

Abstract The present chapter provides details about the aspects related to homology modeling and their structural validation of drug targets in Brucella militensis 16M through in silico analysis. In the present chapter, 12 drug targets were selected which include transcription termination factor, malate synthase G, 3-phosphoshikimate1-carboxyvinyltransferase, isocitrate lyase, carboxynospermidine decarboxylase, nicotinate phosphoribosyltransferase, 2,3,4,5-tetrahydropyridine-2-carboxylate N-succinyltransferase, Iron (III)-binding periplasmic protein precursor, nitrate reductase beta chain, nitric-oxide reductase subunit B, hypothetical protein, and urease accessory protein. The structures of selected drug targets were designed using homology modeling tool, MODELLER. After homology modeling, the molecular models were subjected to structural validation tools using Structural Analysis and Verification Server program, SAVES. The stereochemical qualities of modeled proteins was checked using PROCHECK, and ERRAT. The structural stability of all modeled proteins were determined by ramachandran plot. Further, the modeled potential drug targets accuracy was tested with ProSA analysis to verify the quality of the modeled proteins. ProSA calculated the z-score of protein which based on known structure from all available protein of different sources including X-ray and NMR. The good quality modeled proteins of Brucella melitensis 16M deposited in PMDB database.