title: QM/MM MD simulations of La(III)-phosphopeptide complexes.
abstract: Several bioanalytical enrichment techniques are based on the interactions of phosphopeptides with Ln(III) ions. In order to gain an improved understanding of these complexes and the respective ion-peptide interactions, hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations of La(III) coordinating to the phosphopeptide VPQLEIVPNSpAEER were conducted. Simulations of di- as well as monoanionic phosphate groups were carried out. The La(III) ion and its first hydration layer, including the sidechain of the phosphoserine residue were treated quantum mechanically at RI-MP2/triple zeta level, whereas the remaining part of the system was treated with classical potentials. The simulation of the dianionic phosphopeptide revealed a 9-fold coordinated La(III) ion, with the phosphopeptide binding bi- as well as monodentate. The mean residence times (τ) of the first shell water molecules were 82 ps and 37 ps for the bi- and monodentate complexes, respectively, which is much higher compared to free La(III) in aqueous solution (τ=17 ps). The simulation of the monoanionic La(III)-phosphopeptide complex revealed a bidentate coordination throughout the 80 ps sampling period. An intramolecular hydrogen bond between the hydrogen of the phosphate group and the backbone was observed and a τ value of 14 ps was obtained, which is much lower as for the dianionic complex.
authors.affiliation: Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Christoph B
authors.initials: CB
authors.lastname: Messner
authors.forename: Günther K
authors.initials: GK
authors.lastname: Bonn
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Hofer
mesh_terms: D007811:Lanthanum / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010748:Phosphopeptides / Q000737:chemistry*; D011485:Protein Binding; D011789:Quantum Theory
chemical_list: D010748:Phosphopeptides; D007811:Lanthanum