Influence of Protein-Solvent Interactions on the Molecular Dynamics of Reduced Point Charge Models of Proteins - COMP5

Research output: Contribution in Book/Catalog/Report/Conference proceedingConference contribution

Abstract

We investigate the influence of various solvent models on the structural stability and the protein-water interface of three Ubiquitin complexes (PDB access codes: 1Q0W, 2MBB, 2G3Q) modelled using Amber99sb with two different point charge distributions. A previously developed reduced point charge model (RPCM), where 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 water molecules, involving either a correction of the Lennard-Jones protein-Owater interaction parameters or the coarse-grain SIRAH water description. Molecular Dynamics (MD) simulation conditions are first refined for complex 1Q0W, whose ligand is a single helix structure that has the ability to bend due to a low α-propensity region occurring in its amino acid sequence. Results are further confirmed by MD simulations carried out on complexes 2MBB and 2G3Q.
MD results show that the best agreements between the RPCM and AA models are obtained when using the TIP4P-Ew water force field (FF) with a correction factor γ = 0.7. At the RPCM level, a decrease in γ, or the consideration of SIRAH solvent particles, allow to weaken the protein-solvent interactions. It results in a slight collapse of the protein 3D structure and a less dense hydration shell, thus involving a decrease in the protein-water and water-water H-bonds. The dynamics of the surface protein atoms and of the water shell molecules is also slightly refrained, thus allowing to generate stable RPCM trajectories, at a reduced computational cost. Conversely, solvation conditions such as the uncorrected TIP4P-Ew FF favor the unfolding of protein RPCMs. Interestingly, deconstructed structures appear to be stable when simulated back at the AA level, as illustrated for system 1Q0W.
LanguageEnglish
Title of host publicationAbstracts of the 255th Annual Meeting and Exposition of the American Chemical Society
PublisherACS
Publication statusPublished - 2018
Event255th ACS National Meeting & Exposition - New Orleans, LA, United States
Duration: 18 Mar 201822 Mar 2018

Meeting

Meeting255th ACS National Meeting & Exposition
CountryUnited States
CityNew Orleans, LA
Period18/03/1822/03/18

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Molecular dynamics
Water
Proteins
Atoms
Amino Acids
Molecules
Charge distribution
Solvation
Computer simulation
Ubiquitin
Hydration
Membrane Proteins
Trajectories
Ligands
Costs

Cite this

Leherte, L., & Vercauteren, D. (2018). Influence of Protein-Solvent Interactions on the Molecular Dynamics of Reduced Point Charge Models of Proteins - COMP5. In Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society ACS.
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abstract = "We investigate the influence of various solvent models on the structural stability and the protein-water interface of three Ubiquitin complexes (PDB access codes: 1Q0W, 2MBB, 2G3Q) modelled using Amber99sb with two different point charge distributions. A previously developed reduced point charge model (RPCM), where 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 water molecules, involving either a correction of the Lennard-Jones protein-Owater interaction parameters or the coarse-grain SIRAH water description. Molecular Dynamics (MD) simulation conditions are first refined for complex 1Q0W, whose ligand is a single helix structure that has the ability to bend due to a low α-propensity region occurring in its amino acid sequence. Results are further confirmed by MD simulations carried out on complexes 2MBB and 2G3Q.MD results show that the best agreements between the RPCM and AA models are obtained when using the TIP4P-Ew water force field (FF) with a correction factor γ = 0.7. At the RPCM level, a decrease in γ, or the consideration of SIRAH solvent particles, allow to weaken the protein-solvent interactions. It results in a slight collapse of the protein 3D structure and a less dense hydration shell, thus involving a decrease in the protein-water and water-water H-bonds. The dynamics of the surface protein atoms and of the water shell molecules is also slightly refrained, thus allowing to generate stable RPCM trajectories, at a reduced computational cost. Conversely, solvation conditions such as the uncorrected TIP4P-Ew FF favor the unfolding of protein RPCMs. Interestingly, deconstructed structures appear to be stable when simulated back at the AA level, as illustrated for system 1Q0W.",
author = "Laurence Leherte and Daniel Vercauteren",
year = "2018",
language = "English",
booktitle = "Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society",
publisher = "ACS",

}

Leherte, L & Vercauteren, D 2018, Influence of Protein-Solvent Interactions on the Molecular Dynamics of Reduced Point Charge Models of Proteins - COMP5. in Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society. ACS, 255th ACS National Meeting & Exposition, New Orleans, LA, United States, 18/03/18.

Influence of Protein-Solvent Interactions on the Molecular Dynamics of Reduced Point Charge Models of Proteins - COMP5. / Leherte, Laurence; Vercauteren, Daniel.

Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society. ACS, 2018.

Research output: Contribution in Book/Catalog/Report/Conference proceedingConference contribution

TY - GEN

T1 - Influence of Protein-Solvent Interactions on the Molecular Dynamics of Reduced Point Charge Models of Proteins - COMP5

AU - Leherte, Laurence

AU - Vercauteren, Daniel

PY - 2018

Y1 - 2018

N2 - We investigate the influence of various solvent models on the structural stability and the protein-water interface of three Ubiquitin complexes (PDB access codes: 1Q0W, 2MBB, 2G3Q) modelled using Amber99sb with two different point charge distributions. A previously developed reduced point charge model (RPCM), where 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 water molecules, involving either a correction of the Lennard-Jones protein-Owater interaction parameters or the coarse-grain SIRAH water description. Molecular Dynamics (MD) simulation conditions are first refined for complex 1Q0W, whose ligand is a single helix structure that has the ability to bend due to a low α-propensity region occurring in its amino acid sequence. Results are further confirmed by MD simulations carried out on complexes 2MBB and 2G3Q.MD results show that the best agreements between the RPCM and AA models are obtained when using the TIP4P-Ew water force field (FF) with a correction factor γ = 0.7. At the RPCM level, a decrease in γ, or the consideration of SIRAH solvent particles, allow to weaken the protein-solvent interactions. It results in a slight collapse of the protein 3D structure and a less dense hydration shell, thus involving a decrease in the protein-water and water-water H-bonds. The dynamics of the surface protein atoms and of the water shell molecules is also slightly refrained, thus allowing to generate stable RPCM trajectories, at a reduced computational cost. Conversely, solvation conditions such as the uncorrected TIP4P-Ew FF favor the unfolding of protein RPCMs. Interestingly, deconstructed structures appear to be stable when simulated back at the AA level, as illustrated for system 1Q0W.

AB - We investigate the influence of various solvent models on the structural stability and the protein-water interface of three Ubiquitin complexes (PDB access codes: 1Q0W, 2MBB, 2G3Q) modelled using Amber99sb with two different point charge distributions. A previously developed reduced point charge model (RPCM), where 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 water molecules, involving either a correction of the Lennard-Jones protein-Owater interaction parameters or the coarse-grain SIRAH water description. Molecular Dynamics (MD) simulation conditions are first refined for complex 1Q0W, whose ligand is a single helix structure that has the ability to bend due to a low α-propensity region occurring in its amino acid sequence. Results are further confirmed by MD simulations carried out on complexes 2MBB and 2G3Q.MD results show that the best agreements between the RPCM and AA models are obtained when using the TIP4P-Ew water force field (FF) with a correction factor γ = 0.7. At the RPCM level, a decrease in γ, or the consideration of SIRAH solvent particles, allow to weaken the protein-solvent interactions. It results in a slight collapse of the protein 3D structure and a less dense hydration shell, thus involving a decrease in the protein-water and water-water H-bonds. The dynamics of the surface protein atoms and of the water shell molecules is also slightly refrained, thus allowing to generate stable RPCM trajectories, at a reduced computational cost. Conversely, solvation conditions such as the uncorrected TIP4P-Ew FF favor the unfolding of protein RPCMs. Interestingly, deconstructed structures appear to be stable when simulated back at the AA level, as illustrated for system 1Q0W.

M3 - Conference contribution

BT - Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society

PB - ACS

ER -

Leherte L, Vercauteren D. Influence of Protein-Solvent Interactions on the Molecular Dynamics of Reduced Point Charge Models of Proteins - COMP5. In Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society. ACS. 2018