title: Binding sites and hydrophobic pockets in Human Thioredoxin 1 determined by normal mode analysis.
abstract: The Thioredoxin (Trx) system plays important roles in several diseases (e.g. cancer, viral infections, cardiovascular and neurodegenerative diseases). Therefore, there is a therapeutic interest in the design of modulators of this system. In this work, we used normal mode analysis to identify putative binding site regions for Human Trx1 that arise from global motions. We identified three possible inhibitor's binding regions that corroborate previous experimental findings. We show that intrinsic motions of the protein are related to the exposure of hydrophobic regions and non-active site cysteines that could constitute new binding sites for inhibitors.
authors.affiliation: Laboratório de Biologia Computacional e Bioinformática, Universidade Federal do ABC, Santo André, Brazil.
authors.forename: Eric Allison
authors.initials: EA
authors.lastname: Philot
authors.forename: David
authors.initials: D
authors.lastname: Perahia
authors.forename: Antônio Sérgio Kimus
authors.initials: AS
authors.lastname: Braz
authors.forename: Mauricio Garcia de Souza
authors.initials: MG
authors.lastname: Costa
authors.forename: Luis Paulo Barbour
authors.initials: LP
authors.lastname: Scott
mesh_terms: D000494:Allosteric Regulation; D020134:Catalytic Domain; D055808:Drug Discovery; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D054852:Small Molecule Libraries; D013499:Surface Properties; D013816:Thermodynamics; D013879:Thioredoxins / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D008024:Ligands; D054852:Small Molecule Libraries; D013879:Thioredoxins
keywords: Allosteric inhibition; Binding sites; Human Thioredoxin 1; Molecular modeling; Normal mode analysis