Search

The Matteoli-Mansoori empirical formula is applied for the pair correlation function of simple fluids obeying the Lennard-Jones potential to calculate reduced self-diffusion coefficients on the basis of the modified free volume theory. It is shown that Matteoli-Mansoori empirical formula yields sufficiently accurate self-diffusion coefficients in the supercritical regime, provided that the minimum free volume activating diffusion is estimated with the classical turning point of binary collision at the mean relative kinetic energy.

The density functional theory of transport coefficients are applied to carbon dioxide and the shear viscosity of carbon dioxide s computed without using the empirical approach. The self-diffusion coefficients thus computed are used to compute the density and temperature dependence of the shear viscosity of liquid carbon dioxide by employing the density fluctuation theory formula for shear viscosity.

The shear viscosity formula derived by the density functional theory is computed for argon, krypton, and methane by using the self-diffusion coefficients derived in the modified free volume theory with the help of the generic van der Waals equation. The theory is successfully tested in comparison with experimental data for self-diffusion coefficients and shear viscosity for argon, krypton, and methane.

Influx of ferrous ions from the cytoplasmthrough 3-fold poresin the shell of ferritin protein is computed using a 3-dimensionalPoisson–Nernst–Planck electrodiffusion model, with inputssuch as the pore structure and the diffusivity profile of permeantFe2+ions extracted from all-atom molecular dynamics (MD)simulations. These calculations successfully reproduce experimentalestimates of the transit time of Fe2+through the ferritincoat, which is on the millisecond time scale and hence much too longto be directly simulated via all-atom MD. This is also much longerthan the typical time scale for ion transit in standard membrane spanningion channels whose pores bear structural similarity to that of the3-fold ferritin pore. The slow time scale for Fe2+transportthrough ferritin pores is traced to two features that distinguishthe ferritin pore system from standard ion channels, namely, (i) verylow concentration of cytoplasmic Fe2+under physiologicalconditions and (ii) very small internal diffusion coefficients forions inside the ferritin pore resulting from factors that includethe divalent nature of Fe2+and two rings of negativelycharged amino acids surrounding a narrow geometric obstruction withinthe ferritin pore interior. [ABSTRACT FROM AUTHOR]

The Amyloid-beta protein is related to Alzheimer’sdisease, and various experiments have shown that oligomers as smallas the dimer are cytotoxic. Two alloforms are mainly produced: Aβ1–40and Aβ1–42. They have verydifferent oligomer distributions, and it was recently suggested, fromexperimental studies, that this variation may originate from structuraldifferences in their dimer structures. Little structural informationis available on the Aβ dimer, however, and to complement experimentalobservations, we simulated the folding of the wild-type Aβ1–40and Aβ1–42dimers as wellas the mutated Aβ1–40(D23N) dimer using anaccurate coarse-grained force field coupled to Hamiltonian-temperaturereplica exchange molecular dynamics. The D23N variant impedes thesalt-bridge formation between D23 and K28 seen in the wild-type Aβ,leading to very different fibrillation properties and final amyloidfibrils. Our results show that the Aβ1–42dimerhas a higher propensity than the Aβ1–40dimerto form β-strands at the central hydrophobic core (residues17–21) and at the C-terminal (residues 30–42), whichare two segments crucial to the oligomerization of Aβ. The freeenergy landscape of the Aβ1–42dimer is alsobroader and more complex than that of the Aβ1–40dimer. Interestingly, D23N also impacts the free energy landscapeby increasing the population of configurations with higher β-strandpropensities when compared against Aβ40. In addition,while Aβ1–40(D23N) displays a higher β-strandpropensity at the C-terminal, its solvent accessibility does not changewith respect to the wild-type sequence. Overall, our results showthe strong impact of the two amino acids Ile41-Ala42 and the salt-bridgeD23–K28 on the folding of the Aβ dimer. [ABSTRACT FROM AUTHOR]

We study the mechanism of vacancy migration and phase transitions of 3D crystalline colloidal arrays (CCA) using Langevin dynamics simulations. We calculate the self-diffusion coefficient of the colloid particles and the diffusion constant for vacancies as a function of temperature and DLVO potential parameters. We investigate the phase behavior of several systems with different interaction potential parameters using Voronoi analysis. Voronoi polyhedra tessellation, which is a useful method for characterizing the nearest neighbor environment around each atom, provides an efficient and effective way to identify phase transitions as well as geometrical changes in crystals. Using Voronoi analysis, we show that several neighboring particles are involved in the vacancy migration process that causes the vacancy to diffuse.

The Amyloid-beta protein is related to Alzheimer's disease, and various experiments have shown that oligomers as small as the dimer are cytotoxic. Two alloforms are mainly produced: Aβ(1-40) and Aβ(1-42). They have very different oligomer distributions, and it was recently suggested, from experimental studies, that this variation may originate from structural differences in their dimer structures. Little structural information is available on the Aβ dimer, however, and to complement experimental observations, we simulated the folding of the wild-type Aβ(1-40) and Aβ(1-42) dimers as well as the mutated Aβ(1-40)(D23N) dimer using an accurate coarse-grained force field coupled to Hamiltonian-temperature replica exchange molecular dynamics. The D23N variant impedes the salt-bridge formation between D23 and K28 seen in the wild-type Aβ, leading to very different fibrillation properties and final amyloid fibrils. Our results show that the Aβ(1-42) dimer has a higher propensity than the Aβ(1-40) dimer to form β-strands at the central hydrophobic core (residues 17-21) and at the C-terminal (residues 30-42), which are two segments crucial to the oligomerization of Aβ. The free energy landscape of the Aβ(1-42) dimer is also broader and more complex than that of the Aβ(1-40) dimer. Interestingly, D23N also impacts the free energy landscape by increasing the population of configurations with higher β-strand propensities when compared against Aβ(40). In addition, while Aβ(1-40)(D23N) displays a higher β-strand propensity at the C-terminal, its solvent accessibility does not change with respect to the wild-type sequence. Overall, our results show the strong impact of the two amino acids Ile41-Ala42 and the salt-bridge D23-K28 on the folding of the Aβ dimer.

The loss of the insulin-producing β-cells in the pancreatic islets of Langerhans, responsible for type-II diabetes, is associated with islet amyloid deposits. The main component of these deposits is the amyloid fibrils formed by the 37-residue human islet amyloid polypeptide (hIAPP also known as amylin). Although the fibrils are well characterized by cross β structure, the structure of the transient oligomers formed in the early stage of aggregation remains elusive. In this study, we apply the Hamiltonian-temperature replica exchange molecular dynamics to characterize the structure and thermodynamics of a full-length hIAPP dimer in both the presence and the absence of the Cys2-Cys7 disulfide bond. We compare these results with those obtained on the monomeric and dimeric forms of rat IAPP (rIAPP) with a disulfide bridge which differ from the hIAPP by 6 amino acids in the C-terminal region, but it is unable to form fibrils. Using a coarse-grained protein force field (OPEP-the Optimized Potential for Efficient peptide structure Prediction) running for a total of 10-28 μs per system studied, we show that sequences sample α-helical structure in the N-terminal region but that the length of this secondary element is shorter and less stable for the chains without the disulfide bridge (residues 5-16 for hIAPP with the bridge vs 10-16 for hIAPP without the bridge). This α-helix is known to be an important transient stage in the formation of oligomers. In the C-terminal, the amyloidogenic region of hIAPP, β-strands are seen for residues 17-26 and 30-35. On the contrary, no significant β-sheet content in the C-terminal is observed for either the monomeric or the dimeric rIAPP. These numerical results are fully consistent with recent experimental findings that the N-terminal residues are not part of the fibril by forming α-helical structure but rather play a significant role in stabilizing the amyloidogenic region available for the fibrillation.

Current approaches aimed at determining the free energy surface of all-atom medium-size proteins in explicit solvent are slow and are not sufficient to converge to equilibrium properties. To ensure a proper sampling of the configurational space, it is preferable to use reduced representations such as implicit solvent and/or coarse-grained protein models, which are much lighter computationally. Each model must be verified, however, to ensure that it can recover experimental structures and thermodynamics. Here we test the coarse-grained implicit solvent OPEP model with replica exchange molecular dynamics (REMD) on six peptides ranging in length from 10 to 28 residues: two alanine-based peptides, the second beta-hairpin from protein G, the Trp-cage and zinc-finger motif, and a dimer of a coiled coil peptide. We show that REMD-OPEP recovers the proper thermodynamics of the systems studied, with accurate structural description of the beta-hairpin and Trp-cage peptides (within 1-2 A from experiments). The light computational burden of REMD-OPEP, which enables us to generate many hundred nanoseconds at each temperature and fully assess convergence to equilibrium ensemble, opens the door to the determination of the free energy surface of larger proteins and assemblies.

In this paper, we apply the Matteoli-Mansoori empirical formula for the pair correlation function of simple fluids obeying the Lennard-Jones potential to calculate reduced self-diffusion coefficients on the basis of the modified free volume theory. The self-diffusion coefficient thus computed as functions of temperature and density is compared with the molecular dynamics simulation data and the self-diffusion coefficient obtained by the modified free volume theory implemented with the Monte Carlo simulation method for the pair correlation function. We show that the Matteoli-Mansoori empirical formula yields sufficiently accurate self-diffusion coefficients in the supercritical regime, provided that the minimum free volume activating diffusion is estimated with the classical turning point of binary collision at the mean relative kinetic energy 3k(B)T/2, where k(B) is the Boltzmann constant and T is the temperature. In the subcritical regime, the empirical formula yields qualitatively correct, but lower values for the self-diffusion coefficients compared with computer simulation values and those from the modified free volume theory implemented with the Monte Carlo simulations for the pair correlation function. However, with a slightly modified critical free volume, the results can be made quite acceptable.