title: Probing Polyoxometalate-Protein Interactions Using Molecular Dynamics Simulations.
abstract: The molecular interactions between the CeIV-substituted Keggin anion [PW11O39Ce(OH2)4]3-(CeK) and hen egg-white lysozyme (HEWL) were investigated by molecular dynamics simulations. The analysis of CeK was compared with the CeIV-substituted Keggin dimer [(PW11O39)2Ce]10-(CeK2) and the ZrIV-substituted Lindqvist anion [W5O18Zr(OH2)(OH)]3-(ZrL) to understand how POM features such as shape, size, charge, or type of incorporated metal ion influence the POM⋅⋅⋅protein interactions. Simulations revealed two regions of the protein in which the CeK anion interacts strongly: cationic sites formed by Arg21 and by Arg45 and Arg68. The POMs chiefly interact with the side chains of the positively charged (arginines, lysines) and the polar uncharged residues (tyrosines, serines, aspargines) via electrostatic attraction and hydrogen bonding with the oxygen atoms of the POM framework. The CeK anion shows higher protein affinity than the CeK2and ZrL anions, because it is less hydrophilic and it has the right size and shape for establishing interactions with several residues simultaneously. The larger, more negatively charged CeK2anion has a high solvent-accessible surface, which is sub-optimal for the interaction, while the smaller ZrL anion is highly hydrophilic and cannot efficiently interact with several residues simultaneously.
authors.affiliation: Departament de Química Física i Inorgànica, Universitat Rovira i Virgili, Marcel⋅lí Domingo, 1, 43007, Tarragona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Solé-Daura
authors.affiliation: Laboratory of Bioinorganic Chemistry, KU Leuven, Celestijnenlaan 200F, 3001, Heverlee, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Goovaerts
authors.affiliation: Laboratory of Bioinorganic Chemistry, KU Leuven, Celestijnenlaan 200F, 3001, Heverlee, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Stroobants
authors.affiliation: Laboratory of Bioinorganic Chemistry, KU Leuven, Celestijnenlaan 200F, 3001, Heverlee, Belgium.
authors.forename: Gregory
authors.initials: G
authors.lastname: Absillis
authors.affiliation: Departament de Química Física i Inorgànica, Universitat Rovira i Virgili, Marcel⋅lí Domingo, 1, 43007, Tarragona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Jiménez-Lozano
authors.affiliation: Departament de Química Física i Inorgànica, Universitat Rovira i Virgili, Marcel⋅lí Domingo, 1, 43007, Tarragona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Poblet
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Hirst
authors.affiliation: Laboratory of Bioinorganic Chemistry, KU Leuven, Celestijnenlaan 200F, 3001, Heverlee, Belgium.
authors.forename: Tatjana N
authors.initials: TN
authors.lastname: Parac-Vogt
authors.affiliation: Departament de Química Física i Inorgànica, Universitat Rovira i Virgili, Marcel⋅lí Domingo, 1, 43007, Tarragona, Spain. j.carbo@urv.cat.
authors.forename: Jorge J
authors.initials: JJ
authors.lastname: Carbó
keywords: DFT calculations; molecular dynamics; peptide hydrolysis; polyoxometalates; proteins