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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: In classical simulations, they are typically described as simple van der Waals spheres, making it difficult to provide reliable force field descriptions for them.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

Schematic illustration of the dummy model.12 Instead of a simple sphere, the point chargeof the metal ion isdistributed to six dummy atoms with partial charge δ+.
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fig1: Schematic illustration of the dummy model.12 Instead of a simple sphere, the point chargeof the metal ion isdistributed to six dummy atoms with partial charge δ+.

Mentions: Molecular dynamics (MD)simulations are commonly applied to investigatethe dynamics and structural information of protein systems includingmetalloproteins. However, most of the widely used force fields donot have appropriate parameters for metal ions, presenting a practicalobstacle to MD studies of metalloproteins. Various approaches havebeen developed to describe the interactions between metal ions andcoordinated residues in classical MD simulations. They include representationsof metal ions as simple van der Waals spheres,7,8 nonbondedmodels with dummy atoms (called “dummy models” henceforth),9−13 and bonded models where artificial bonds between metal ions andligands are introduced.14−17 Each of these methods has its own merits and limitations.16,18 Modeling metal ions as simple spheres with electrostatic and vander Waals interactions is often successful for the description ofalkali and alkaline-earth ions, but appears to be inadequate whenit comes to more complex situations such as systems containing multinuclearmetal centers with closely located metal ions, or for the correcttreatment of transition metals. Bonded models, on the other hand,suffer from the fact that they include predefined covalent bonds betweenthe metal and ligands, thus not allowing for ligand exchange and/orinterconversion between different coordination geometries. For a morethorough discussion of the pros and cons of these approaches, thereader is referred to ref (13) and the references therein. The dummy model approach aimsat resolving the aforementioned problems by providing a nonbondeddescription that captures both structural and electrostatic effectsvia the introduction of dummy atoms surrounding the metal ion. Therehave been several studies reporting dummy models for Zn2+, Ca2+, Mg2+, Fe2+, Ni2+, Co2+, and Mn2+ in tetrahedral, octahedral,or pentagonal bipyramid geometries.9−13 For the octahedral model shown in Figure 1, originally proposed by Åqvist and Warshel,12 six dummy atoms with negligible van der Waalsparameters and positive charge δ+ are placed arounda central metal ion (n+) with a chargeof n – 6δ. Such a charge distributionis particularly advantageous in systems with multiple metal centers,10 since the redistribution of charges reducesthe excessive repulsion between metal sites. The dummy atoms are bondedand angled to the central atom, but there are no bonds to the ligands.No dummy model has yet been developed for Cu2+, most likelybecause of the Jahn–Teller distortion of Cu2+ (electronconfiguration d9) in water. In the present work, a Cu2+ dummy model (CuDum) that includes the Jahn–Tellereffect is developed to facilitate computational studies of copperproteins.19 The major strength of thismodel is that it allows us to simultaneously reproduce the correctcoordination properties of the metal, without the need for higherlevel quantum chemical calculations, while sampling the conformationalproperties of the peptide.20 It shouldbe noted that recently a polarizable force field for transition-metalions was developed based on AMOEBA and the angular overlap model (AOM).21 This classical approach, which is similar inidea to previous AOM implementations for Cu2+,22,23 can also handle the Jahn–Teller distortion yet is computationallymore costly than the dummy model approach. Our CuDum model is implementedinto the MD program Gromacs,24 togetherwith the previous Zn2+ dummy model (ZnDum),13 which was originally developed for Q.25


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)

Schematic illustration of the dummy model.12 Instead of a simple sphere, the point chargeof the metal ion isdistributed to six dummy atoms with partial charge δ+.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Schematic illustration of the dummy model.12 Instead of a simple sphere, the point chargeof the metal ion isdistributed to six dummy atoms with partial charge δ+.
Mentions: Molecular dynamics (MD)simulations are commonly applied to investigatethe dynamics and structural information of protein systems includingmetalloproteins. However, most of the widely used force fields donot have appropriate parameters for metal ions, presenting a practicalobstacle to MD studies of metalloproteins. Various approaches havebeen developed to describe the interactions between metal ions andcoordinated residues in classical MD simulations. They include representationsof metal ions as simple van der Waals spheres,7,8 nonbondedmodels with dummy atoms (called “dummy models” henceforth),9−13 and bonded models where artificial bonds between metal ions andligands are introduced.14−17 Each of these methods has its own merits and limitations.16,18 Modeling metal ions as simple spheres with electrostatic and vander Waals interactions is often successful for the description ofalkali and alkaline-earth ions, but appears to be inadequate whenit comes to more complex situations such as systems containing multinuclearmetal centers with closely located metal ions, or for the correcttreatment of transition metals. Bonded models, on the other hand,suffer from the fact that they include predefined covalent bonds betweenthe metal and ligands, thus not allowing for ligand exchange and/orinterconversion between different coordination geometries. For a morethorough discussion of the pros and cons of these approaches, thereader is referred to ref (13) and the references therein. The dummy model approach aimsat resolving the aforementioned problems by providing a nonbondeddescription that captures both structural and electrostatic effectsvia the introduction of dummy atoms surrounding the metal ion. Therehave been several studies reporting dummy models for Zn2+, Ca2+, Mg2+, Fe2+, Ni2+, Co2+, and Mn2+ in tetrahedral, octahedral,or pentagonal bipyramid geometries.9−13 For the octahedral model shown in Figure 1, originally proposed by Åqvist and Warshel,12 six dummy atoms with negligible van der Waalsparameters and positive charge δ+ are placed arounda central metal ion (n+) with a chargeof n – 6δ. Such a charge distributionis particularly advantageous in systems with multiple metal centers,10 since the redistribution of charges reducesthe excessive repulsion between metal sites. The dummy atoms are bondedand angled to the central atom, but there are no bonds to the ligands.No dummy model has yet been developed for Cu2+, most likelybecause of the Jahn–Teller distortion of Cu2+ (electronconfiguration d9) in water. In the present work, a Cu2+ dummy model (CuDum) that includes the Jahn–Tellereffect is developed to facilitate computational studies of copperproteins.19 The major strength of thismodel is that it allows us to simultaneously reproduce the correctcoordination properties of the metal, without the need for higherlevel quantum chemical calculations, while sampling the conformationalproperties of the peptide.20 It shouldbe noted that recently a polarizable force field for transition-metalions was developed based on AMOEBA and the angular overlap model (AOM).21 This classical approach, which is similar inidea to previous AOM implementations for Cu2+,22,23 can also handle the Jahn–Teller distortion yet is computationallymore costly than the dummy model approach. Our CuDum model is implementedinto the MD program Gromacs,24 togetherwith the previous Zn2+ dummy model (ZnDum),13 which was originally developed for Q.25

Bottom Line: In classical simulations, they are typically described as simple van der Waals spheres, making it difficult to provide reliable force field descriptions for them.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