title: Molecular modeling of bioorganometallic compounds: thermodynamic properties of molybdocene-glutathione complexes and mechanism of Peptide hydrolysis.
abstract: The computational study of bioinorganic complexes between transition metals and flexible ligands is still challenging, given that, besides requiring extensive conformational searches, the treatment of metal-ligand bonds demands the application of quantum chemical methods. Herein, the adducts formed between molybdocene, which exhibits antitumor activity and reacts with thiol groups to give stable water-soluble complexes, and the tripeptide glutathione, which is a major source of biological thiols, are studied. Conformational searches are performed using the semiempirical PM6 method followed by geometry optimizations and single-point calculations using density functional theory methods. In addition, molecular dynamics simulations of the molybdocene-glutathione complex involved in the regioselective hydrolysis of the Cys-Gly linkage are performed in explicit solvent. The reactive process is also studied theoretically on cluster models of both the molybdocene-bound and the free peptide.
authors: Departamento de Química Física y Analítica, Universidad de Oviedo, Julián Clavería 8, 33006 Oviedo (Spain). dimas@uniovi.es.
authors: Dimas
authors: D
authors: Suárez
authors: Departamento de Química Física y Analítica, Universidad de Oviedo, Julián Clavería 8, 33006 Oviedo (Spain).
authors: Natalia
authors: N
authors: Díaz
mesh_terms: D005978:Glutathione / Q000737:chemistry*; D006868:Hydrolysis; D056004:Molecular Dynamics Simulation; D009942:Organometallic Compounds / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D009942:Organometallic Compounds; D010455:Peptides; C024389:molybdocene dichloride; D005978:Glutathione
keywords: density functional calculations; molecular modeling; organometallic compounds; peptides; semiempirical calculations