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Development and Application of a Nonbonded Cu(2+) Model That Includes the Jahn-Teller Effect.

Liao Q, Kamerlin SC, Strodel B - J Phys Chem Lett (2015)

Bottom Line: This challenge is addressed in the current study, where, for the first time, a dummy model including a Jahn-Teller effect is developed for Cu(2+).We successfully validate its usefulness by studying metal binding in two biological systems: the amyloid-β peptide and the mixed-metal enzyme superoxide dismutase.We believe that our parameters will be of significant value for the computational study of Cu(2+)-dependent biological systems using classical models.

View Article: PubMed Central - PubMed

ABSTRACT
Metal ions are both ubiquitous to and crucial in biology. In classical simulations, they are typically described as simple van der Waals spheres, making it difficult to provide reliable force field descriptions for them. An alternative is given by nonbonded dummy models, in which the central metal atom is surrounded by dummy particles that each carry a partial charge. While such dummy models already exist for other metal ions, none is available yet for Cu(2+) because of the challenge to reproduce the Jahn-Teller distortion. This challenge is addressed in the current study, where, for the first time, a dummy model including a Jahn-Teller effect is developed for Cu(2+). We successfully validate its usefulness by studying metal binding in two biological systems: the amyloid-β peptide and the mixed-metal enzyme superoxide dismutase. We believe that our parameters will be of significant value for the computational study of Cu(2+)-dependent biological systems using classical models.

No MeSH data available.


Related in: MedlinePlus

Final snapshots of dummy models in proteinsystems taken from 100ns MD simulations of (a) Aβ1–16E11/ZnDum, (b) Aβ1–16E11/CuDum, (c) Aβ1–16A2/CuDum,and (d) CuZnSOD/ZnDum/CuDum. The proteins are shown in cartoon presentationand colored red for β-sheet, purple for 310 helix,yellow for turn, and white for coil. The N- and C-terminus of Aβ1–16 is indicated by a blue and red bead, respectively.The metal binding sites are shown in Corey–Pauling–Koltun(CPK) presentation using turquoise for C, blue for N, red for O, andwhite for H atoms, while Zn2+ is shown in gray and Cu2+ in orange.
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fig2: Final snapshots of dummy models in proteinsystems taken from 100ns MD simulations of (a) Aβ1–16E11/ZnDum, (b) Aβ1–16E11/CuDum, (c) Aβ1–16A2/CuDum,and (d) CuZnSOD/ZnDum/CuDum. The proteins are shown in cartoon presentationand colored red for β-sheet, purple for 310 helix,yellow for turn, and white for coil. The N- and C-terminus of Aβ1–16 is indicated by a blue and red bead, respectively.The metal binding sites are shown in Corey–Pauling–Koltun(CPK) presentation using turquoise for C, blue for N, red for O, andwhite for H atoms, while Zn2+ is shown in gray and Cu2+ in orange.

Mentions: Full details about the MD simulationsperformed in this work andthe adaptation of ZnDum for its use in Gromacs are given in the Supporting Information (SI). In short, the vander Waals distance σZnO was systematically optimized(Table S1) in oder to reproduce both theexperimental ion-oxygen distance (Zn–O) and the hydration freeenergy (ΔGhyd)for Zn2+ in water. The calculation of ΔGhyd is divided in two steps, decomposingit into the contributions from van der Waals (ΔGLJ) and electrostatic (ΔGelec) interactions7,26,27 (Figure S1). For σZnO = 2.034 Å, we found a compromisein terms of reproducing both ΔGhyd and Zn–O with good accuracy (Figure S2). Furthermore, in subsequent 100 ns MD simulationsfor Aβ1–16 in complex with ZnDum the metalbinding site was maintained in a distorted square pyrimidal geometry(Figure 2a), in accordance with the NMR structure(PDB ID: 1ZE9).28


Development and Application of a Nonbonded Cu(2+) Model That Includes the Jahn-Teller Effect.

Liao Q, Kamerlin SC, Strodel B - J Phys Chem Lett (2015)

Final snapshots of dummy models in proteinsystems taken from 100ns MD simulations of (a) Aβ1–16E11/ZnDum, (b) Aβ1–16E11/CuDum, (c) Aβ1–16A2/CuDum,and (d) CuZnSOD/ZnDum/CuDum. The proteins are shown in cartoon presentationand colored red for β-sheet, purple for 310 helix,yellow for turn, and white for coil. The N- and C-terminus of Aβ1–16 is indicated by a blue and red bead, respectively.The metal binding sites are shown in Corey–Pauling–Koltun(CPK) presentation using turquoise for C, blue for N, red for O, andwhite for H atoms, while Zn2+ is shown in gray and Cu2+ in orange.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4493862&req=5

fig2: Final snapshots of dummy models in proteinsystems taken from 100ns MD simulations of (a) Aβ1–16E11/ZnDum, (b) Aβ1–16E11/CuDum, (c) Aβ1–16A2/CuDum,and (d) CuZnSOD/ZnDum/CuDum. The proteins are shown in cartoon presentationand colored red for β-sheet, purple for 310 helix,yellow for turn, and white for coil. The N- and C-terminus of Aβ1–16 is indicated by a blue and red bead, respectively.The metal binding sites are shown in Corey–Pauling–Koltun(CPK) presentation using turquoise for C, blue for N, red for O, andwhite for H atoms, while Zn2+ is shown in gray and Cu2+ in orange.
Mentions: Full details about the MD simulationsperformed in this work andthe adaptation of ZnDum for its use in Gromacs are given in the Supporting Information (SI). In short, the vander Waals distance σZnO was systematically optimized(Table S1) in oder to reproduce both theexperimental ion-oxygen distance (Zn–O) and the hydration freeenergy (ΔGhyd)for Zn2+ in water. The calculation of ΔGhyd is divided in two steps, decomposingit into the contributions from van der Waals (ΔGLJ) and electrostatic (ΔGelec) interactions7,26,27 (Figure S1). For σZnO = 2.034 Å, we found a compromisein terms of reproducing both ΔGhyd and Zn–O with good accuracy (Figure S2). Furthermore, in subsequent 100 ns MD simulationsfor Aβ1–16 in complex with ZnDum the metalbinding site was maintained in a distorted square pyrimidal geometry(Figure 2a), in accordance with the NMR structure(PDB ID: 1ZE9).28

Bottom Line: This challenge is addressed in the current study, where, for the first time, a dummy model including a Jahn-Teller effect is developed for Cu(2+).We successfully validate its usefulness by studying metal binding in two biological systems: the amyloid-β peptide and the mixed-metal enzyme superoxide dismutase.We believe that our parameters will be of significant value for the computational study of Cu(2+)-dependent biological systems using classical models.

View Article: PubMed Central - PubMed

ABSTRACT
Metal ions are both ubiquitous to and crucial in biology. In classical simulations, they are typically described as simple van der Waals spheres, making it difficult to provide reliable force field descriptions for them. An alternative is given by nonbonded dummy models, in which the central metal atom is surrounded by dummy particles that each carry a partial charge. While such dummy models already exist for other metal ions, none is available yet for Cu(2+) because of the challenge to reproduce the Jahn-Teller distortion. This challenge is addressed in the current study, where, for the first time, a dummy model including a Jahn-Teller effect is developed for Cu(2+). We successfully validate its usefulness by studying metal binding in two biological systems: the amyloid-β peptide and the mixed-metal enzyme superoxide dismutase. We believe that our parameters will be of significant value for the computational study of Cu(2+)-dependent biological systems using classical models.

No MeSH data available.


Related in: MedlinePlus