<i>Understanding Molecular Simulation: From Algorithms to Applications</i>

Frenkel, Daan; Smit, Berend

doi:10.1063/1.881812

Cited by 5,607 publications

(9,180 citation statements)

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“…53,54 The particle mesh Ewald method with a cutoff value of 450 Å was used to treat the long-range interactions, and bonds were constrained using the SHAKE algorithm. 53,54 Based on the cumulative secondary structure abundance, 37,38 we concluded that both the wildtype and A30P mutant-type αS simulations reached convergence after 20 ns of simulation per replica (see the Supporting Information). The structural and thermodynamic properties of the structures obtained after convergence were calculated for the replica closest to physiological temperature (310 K).…”

Section: ■ Methodsmentioning

confidence: 99%

Structures and Free Energy Landscapes of the Wild-Type and A30P Mutant-Type α-Synuclein Proteins with Dynamics

Wise-Scira¹,

Aloglu²,

Dunn³

et al. 2013

ACS Chem. Neurosci.

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The genetic missense A30P mutation of the wild-type α-synuclein protein results in the replacement of the 30th amino acid residue from alanine (Ala) to proline (Pro) and was initially found in the members of a German family who developed Parkinson's disease. Even though the structures of these proteins have been measured before, detailed understanding about the structures and their relationships with free energy landscapes is lacking, which is of interest to provide insights into the pathogenic mechanism of Parkinson's disease. We report the secondary and tertiary structures and conformational free energy landscapes of the wild-type and A30P mutant-type α-synuclein proteins in an aqueous solution environment via extensive parallel tempering molecular dynamics simulations along with thermodynamic calculations. In addition, we present the residual secondary structure component transition stabilities at the atomic level with dynamics in terms of free energy change calculations using a new strategy that we reported most recently. Our studies yield new interesting results; for instance, we find that the A30P mutation has local as well as long-range effects on the structural properties of the wild-type α-synuclein protein. The helical content at Ala18-Gly31 is less prominent in comparison to the wild-type α-synuclein protein. The β-sheet structure abundance decreases in the N-terminal region upon A30P mutation of the wild-type α-synuclein, whereas the NAC and C-terminal regions possess larger tendencies for β-sheet structure formation. Long-range intramolecular protein interactions are less abundant upon A30P mutation, especially between the NAC and C-terminal regions, which is linked to the less compact and less stable structures of the A30P mutant-type rather than the wild-type α-synuclein protein. Results including the usage of our new strategy for secondary structure transition stabilities show that the A30P mutant-type α-synuclein tendency toward aggregation is higher than the wild-type α-synuclein but we also find that the C-terminal and NAC regions of the A30P mutant-type α-synuclein are reactive toward fibrillzation and aggregation based on atomic level studies with dynamics in an aqueous solution environment. Therefore, we propose that small molecules or drugs blocking the specific residues, which we report herein, located in the NAC-and C-terminal regions of the A30P mutant-type α-synuclein protein might help to reduce the toxicity of the A30P mutant-type α-synuclein protein.

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Section: ■ Methodsmentioning

confidence: 99%

Structures and Free Energy Landscapes of the Wild-Type and A30P Mutant-Type α-Synuclein Proteins with Dynamics

Wise-Scira¹,

Aloglu²,

Dunn³

et al. 2013

ACS Chem. Neurosci.

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“…Minimum image conditions were used. 63 In the simulation, one 5 ns NPT ensemble equilibration was first carried out. The temperature was kept at 300 K by weakly coupling the system to the Berendsen thermostats 64 with the relaxation time of 0.1 ps.…”

Section: Methodsmentioning

confidence: 99%

Effect of Ion Pairing on the Solution Dynamics Investigated by the Simulations of the Optical Kerr Effect and the Dielectric Relaxation Spectra

Zhang

Zhuang

2013

J. Phys. Chem. B

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ABSTRACT:The optical Kerr effect (OKE) and dielectric relaxation spectroscopy (DRS) signals of MgCl 2 aqueous solutions were modeled based on the same group of molecular dynamics simulation trajectories. Plausible agreement between the simulations and the experiments allows us to analyze the microscopic origin of the different concentration dependences of relaxation times probed by these two techniques. Our simulations suggest that a significant amount of cations and anions associate in the solutions due to the ion pairing effect. These ion assemblies as well as the free cations form suspending clusters together with the water molecules in their cation hydration shells. The dynamics of water molecules in these clusters is significantly hindered, while that of other water molecules remains largely unaffected. The relaxation times measured by OKE and DRS have different concentration dependences because DRS probes only the rotational dynamics of water molecules outside of the cluster while OKE contains the information of dynamics of all of the water molecules in the solutions. Such findings provide us a microscopic picture on how the ion hydration affects the water dynamics in certain ionic solutions in which ion pairing plays an important role.

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“…Molecular dynamics simulation represent a system by N interaction particles [44]. At any time, the state of the system is given by (r i , v i ), where r i and v i are the position and velocity of particle i in the system.…”

Section: Basics and Techniquesmentioning

confidence: 99%

Effect of Cross-Linking on the Diffusion of Water, Ions, and Small Molecules in Hydrogels

2009

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Understanding the diffusion of small molecules in hydrogel system is of major importance in a variety of applications including drug delivery systems, tissue engineering and contact lens. Cross-linking density of hydrogels has been commonly used to tune key parameters like mesh size and molecular weight between cross-linkers, in order to change macroscopic properties of hydrogels. In this thesis, molecular dynamics investigations of chemically-cross-linked poly(ethylene glycol) (PEG) hydrogels are reported with the aim of exploring the diffusion properties of water, ions, and rhodamine within the polymer at the molecular level.The water structure and diffusion properties were studied at various cross-linking densities with molecular weights of the chains ranging from 572 to 3400. As the cross-linking density is increased, the water diffusion decreases and the slowdown in diffusion is more severe at the polymer-water interface. The water diffusion at various cross-linking densities is correlated with the water hydrogen bonding dynamics. The diffusion of ions and rhodamine also decreased as the cross-linking density is increased. The variation of diffusion coefficient with cross-linking density is related to the variation of water content at different cross-linking densities.Comparison of simulation results and obstruction scaling theory for hydrogels showed similar trends.ii To Father and Mother.iii

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Understanding Molecular Simulation: From Algorithms to Applications

Cited by 5,607 publications

References 0 publications

Structures and Free Energy Landscapes of the Wild-Type and A30P Mutant-Type α-Synuclein Proteins with Dynamics

Structures and Free Energy Landscapes of the Wild-Type and A30P Mutant-Type α-Synuclein Proteins with Dynamics

Effect of Ion Pairing on the Solution Dynamics Investigated by the Simulations of the Optical Kerr Effect and the Dielectric Relaxation Spectra

Effect of Cross-Linking on the Diffusion of Water, Ions, and Small Molecules in Hydrogels

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