Reduced Point Charge Models of Proteins - Effect of Protein-Water Interactions in Molecular Dynamics Simulations of Ubiquitin Systems

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Résumé

We investigate the influence of various solvent models on the structural stability and protein-water interface of three Ubiquitin complexes (PDB access codes: 1Q0W, 2MBB, 2G3Q) modeled using the Amber99sb force field (FF) and two different point charge distributions. A previously developed reduced point charge model (RPCM), wherein each amino acid residue is described by a limited number of point charges, is tested and compared to its all-atom (AA) version. The complexes are solvated in TIP4P-Ew or TIP3P type water molecules, involving either the scaling of the Lennard-Jones protein-Owater interaction parameters, or the coarse-grain (CG) SIRAH water description. The best agreements between the RPCM and AA models were obtained for structural, protein-water, and ligand-Ubiquitin properties when using the TIP4P-Ew water FF with a scaling factor γ of 0.7. At the RPCM level, a decrease in γ, or the inclusion of SIRAH particles, allows to weaken the protein-water interactions. It results in a slight collapse of the protein structure and a less compact hydration shell, and thus, in a decrease in the number of protein-water and water-water H-bonds. The dynamics of the surface protein atoms and of the water shell molecules are also slightly refrained, which allow to generate stable RPCM trajectories. 
langueAnglais
Pages9771-9784
Nombre de pages14
journalJournal of Physical Chemistry B
Les DOIs
étatPublié - 2017

Empreinte digitale

Molecular dynamics
Proteins
Computer simulation
Water
Atoms
Molecules
Charge distribution
Hydration
Amino acids
Ligands
Trajectories
Hydrogen

Citer ceci

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title = "Reduced Point Charge Models of Proteins - Effect of Protein-Water Interactions in Molecular Dynamics Simulations of Ubiquitin Systems",
abstract = "We investigate the influence of various solvent models on the structural stability and protein-water interface of three Ubiquitin complexes (PDB access codes: 1Q0W, 2MBB, 2G3Q) modeled using the Amber99sb force field (FF) and two different point charge distributions. A previously developed reduced point charge model (RPCM), wherein each amino acid residue is described by a limited number of point charges, is tested and compared to its all-atom (AA) version. The complexes are solvated in TIP4P-Ew or TIP3P type water molecules, involving either the scaling of the Lennard-Jones protein-Owater interaction parameters, or the coarse-grain (CG) SIRAH water description. The best agreements between the RPCM and AA models were obtained for structural, protein-water, and ligand-Ubiquitin properties when using the TIP4P-Ew water FF with a scaling factor γ of 0.7. At the RPCM level, a decrease in γ, or the inclusion of SIRAH particles, allows to weaken the protein-water interactions. It results in a slight collapse of the protein structure and a less compact hydration shell, and thus, in a decrease in the number of protein-water and water-water H-bonds. The dynamics of the surface protein atoms and of the water shell molecules are also slightly refrained, which allow to generate stable RPCM trajectories. ",
author = "Laurence Leherte and Daniel Vercauteren",
year = "2017",
doi = "10.1021/acs.jpcb.7b06355",
language = "English",
pages = "9771--9784",
journal = "Journal of Physical Chemistry B",
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publisher = "American Chemical Society",

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AU - Leherte,Laurence

AU - Vercauteren,Daniel

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N2 - We investigate the influence of various solvent models on the structural stability and protein-water interface of three Ubiquitin complexes (PDB access codes: 1Q0W, 2MBB, 2G3Q) modeled using the Amber99sb force field (FF) and two different point charge distributions. A previously developed reduced point charge model (RPCM), wherein each amino acid residue is described by a limited number of point charges, is tested and compared to its all-atom (AA) version. The complexes are solvated in TIP4P-Ew or TIP3P type water molecules, involving either the scaling of the Lennard-Jones protein-Owater interaction parameters, or the coarse-grain (CG) SIRAH water description. The best agreements between the RPCM and AA models were obtained for structural, protein-water, and ligand-Ubiquitin properties when using the TIP4P-Ew water FF with a scaling factor γ of 0.7. At the RPCM level, a decrease in γ, or the inclusion of SIRAH particles, allows to weaken the protein-water interactions. It results in a slight collapse of the protein structure and a less compact hydration shell, and thus, in a decrease in the number of protein-water and water-water H-bonds. The dynamics of the surface protein atoms and of the water shell molecules are also slightly refrained, which allow to generate stable RPCM trajectories. 

AB - We investigate the influence of various solvent models on the structural stability and protein-water interface of three Ubiquitin complexes (PDB access codes: 1Q0W, 2MBB, 2G3Q) modeled using the Amber99sb force field (FF) and two different point charge distributions. A previously developed reduced point charge model (RPCM), wherein each amino acid residue is described by a limited number of point charges, is tested and compared to its all-atom (AA) version. The complexes are solvated in TIP4P-Ew or TIP3P type water molecules, involving either the scaling of the Lennard-Jones protein-Owater interaction parameters, or the coarse-grain (CG) SIRAH water description. The best agreements between the RPCM and AA models were obtained for structural, protein-water, and ligand-Ubiquitin properties when using the TIP4P-Ew water FF with a scaling factor γ of 0.7. At the RPCM level, a decrease in γ, or the inclusion of SIRAH particles, allows to weaken the protein-water interactions. It results in a slight collapse of the protein structure and a less compact hydration shell, and thus, in a decrease in the number of protein-water and water-water H-bonds. The dynamics of the surface protein atoms and of the water shell molecules are also slightly refrained, which allow to generate stable RPCM trajectories. 

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