Rafael Najmanovich

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The human cytosolic sulfotransfases (hSULTs) comprise a family of 12 phase II enzymes involved in the metabolism of drugs and hormones, the bioactivation of carcinogens, and the detoxification of xenobiotics. Knowledge of the structural and mechanistic basis of substrate specificity and activity is crucial for understanding steroid and hormone metabolism,(More)
MOTIVATION An increasing number of protein structures are being determined for which no biochemical characterization is available. The analysis of protein structure and function assignment is becoming an unexpected challenge and a major bottleneck towards the goal of well-annotated genomes. As shape plays a crucial role in biomolecular recognition and(More)
The accurate identification of ligand binding sites in protein structures can be valuable in determining protein function. Once the binding site is known, it becomes easier to perform in silico and experimental procedures that may allow the ligand type and the protein function to be determined. For example, binding pocket shape analysis relies heavily on(More)
Contact surface area and chemical properties of atoms are used to concurrently predict conformations of multiple amino acid side chains on a fixed protein backbone. The combination of surface complementarity and solvent-accessible surface accounts for van der Waals forces and solvation free energy. The scoring function is particularly suitable for modeling(More)
ENCoM is a coarse-grained normal mode analysis method recently introduced that unlike previous such methods is unique in that it accounts for the nature of amino acids. The inclusion of this layer of information was shown to improve conformational space sampling and apply for the first time a coarse-grained normal mode analysis method to predict the effect(More)
MOTIVATION Current computational methods for the prediction of function from structure are restricted to the detection of similarities and subsequent transfer of functional annotation. In a significant minority of cases, global sequence or structural (fold) similarities do not provide clues about protein function. In these cases, one alternative is to(More)
Normal mode analysis (NMA) methods are widely used to study dynamic aspects of protein structures. Two critical components of NMA methods are coarse-graining in the level of simplification used to represent protein structures and the choice of potential energy functional form. There is a trade-off between speed and accuracy in different choices. In one(More)
Tuberculosis remains as one of the main cause of mortality worldwide due to a single infectious agent, Mycobacterium tuberculosis. The aroK-encoded M. tuberculosis Shikimate Kinase (MtSK), shown to be essential for survival of bacilli, catalyzes the phosphoryl transfer from ATP to the carbon-3 hydroxyl group of shikimate (SKH), yielding(More)
Human protein kinases play fundamental roles mediating the majority of signal transduction pathways in eukaryotic cells as well as a multitude of other processes involved in metabolism, cell-cycle regulation, cellular shape, motility, differentiation and apoptosis. The human protein kinome contains 518 members. Most studies that focus on the human kinome(More)
Histone methyltransferases (HMTs) transfer a methyl group from the cofactor S-adenosyl methionine to lysine or arginine residues on histone tails, thereby regulating chromatin compaction, binding of effector proteins and gene transcription. HMTs constitute an emerging target class in diverse disease areas, and selective chemical probes are necessary for(More)