Isothermal-isobaric Molecular Dynamics Research Articles

On the composition dependence of the microscopic structure, thermodynamic, dynamic and dielectric properties of water-dimethyl formamide model mixtures. Molecular dynamics simulation results

Isothermal-isobaric molecular dynamics simulations have been performed to examine an ample set of properties of the model water-N,N-dimethylformamide (DMF) mixture as a function of composition. The SPC-E and TIP4P-Ew water models together with two united atom models for DMF [Chalaris M., Samios J., J. Chem. Phys., 2000, 112, 8581; Cordeiro J., Int. J. Quantum Chem., 1997, 65, 709] were used. Our principal analyses concern the behaviour of structural properties in terms of radial distribution functions, and the number of hydrogen bonds between molecules of different species as well as thermodynamic properties. Namely, we explore the density, excess mixing molar volume and enthalpy, the heat capacity and excess mixing heat capacity. Finally, the self-diffusion coefficients of species and the dielectric constant of the system are discussed. In addition, surface tension of water-DMF mixtures has been calculated and analyzed.

Isobaric-isothermal molecular dynamics computer simulations of the properties of water-1,2-dimethoxyethane model mixtures

Isothermal-isobaric molecular dynamics simulations have been performed to examine a broad set of properties of the model water-1,2-dimethoxyethane (DME) mixture as a function of composition. The SPC-E and TIP4P-Ew water models and the modified TraPPE model for DME were applied. Our principal focus was to explore the trends of behaviour of the structural properties in terms of the radial distribution functions, coordination numbers and number of hydrogen bonds between molecules of different species, and of conformations of DME molecules. Thermodynamic properties, such as density, molar volume, enthalpy of mixing and heat capacity at constant pressure have been examined. Finally, the self-diffusion coefficients of species and the dielectric constant of the system were calculated and analyzed.

How fast fast-folding proteins fold in silico

In reported microcanonical molecular dynamics simulations, fast-folding proteins CLN025 and Trp-cage autonomously folded to experimentally determined native conformations. However, the folding times of these proteins derived from the simulations were more than 4–10 times longer than their experimental values. This article reports autonomous folding of CLN025 and Trp-cage in isobaric–isothermal molecular dynamics simulations with agreements within factors of 0.69–1.75 between simulated and experimental folding times at different temperatures. These results show that CLN025 and Trp-cage can now autonomously fold in silico as fast as in experiments, and suggest that the accuracy of folding simulations for fast-folding proteins begins to overlap with the accuracy of folding experiments. This opens new prospects of developing computer algorithms that can predict both ensembles of conformations and their interconversion rates for a protein from its sequence for artificial intelligence on how and when a protein acts as a receiver, switch, and relay to facilitate various subcellular-to-tissue communications. Then the genetic information that encodes proteins can be better read in the context of intricate biological functions.

Molecular dynamics study of water diffusion in an amphiphilic block copolymer with large difference in the blocks’ glass transition temperatures

Isothermal-isobaric molecular dynamics simulation was used to study the diffusion mechanism of water in polyurethane-block-poly(N-isopropyl acrylamide) (PU-block-PNIPAm) with a hydrophobic PU/hydrophilic PNIPAm mass ratio of 1.4 to 1 at 298 K and 450 K. Here, the experimental glass transition temperature (T g ) of PU is 243 K while that of PNIPAm is 383 K. Different amounts of water up to 15 wt-% were added to PU-block-PNIPAm. We were able to reproduce the specific volumes and glass transition temperatures (250 K and 390 K) of PU-block-PNIPAm. The computed self-diffusion coefficient of water increased exponentially with increasing water concentration at both temperatures (i.e., following the free volume model of Fujita). It suggested that water diffusion in PU-block-PNIPAm depends only on its fractional free volume despite the free volume inhomogeneity. It is noted that at 298 K, PU is rubbery while PNIPAm is glassy. Regardless of temperature, radial distribution functions showed that water formed clusters with sizes in the range of 0.2–0.4 nm in PU-block-PNIPAm. At low water concentrations, more clusters were found in the PU domain but at high water concentrations, more in the PNIPAm domain. It is believed that water molecules diffuse as clusters rather than as individual molecules.

Use of molecular dynamics simulations to estimate the solubility of menadione in supercritical CO2 using Chrastil's model

The binary system of menadione in explicit supercritical carbon dioxide (SC-CO2) was studied using molecular dynamics (MD) simulations, with the objective to understand the nature of interactions between menadione and SC-CO2 at different temperatures and pressures in order to complement experimental solubility measurements. A force field was developed for menadione and tested by comparing computed and experimental monoclinic crystal structures at 283 K and 0.01 MPa. Lattice parameters obtained from anisotropic isothermal-isobaric MD simulations agreed reasonably well with experimental values, with an average absolute relative deviation (AARD%) less than 7%. A previously validated force field for SC-CO2 was used, and simple mixing rules were used to describe cross interactions. Canonical ensemble MD simulations were used to estimate the association number for CO2 about menadione and the enthalpy required to form a SC-CO2 solvate complex with menadione as a function of temperature and CO2 density. Spatial distribution functions were computed to better understand the nature of the molecular-level interactions between menadione and SC-CO2 as well as between associating menadione molecules. This work is the first part of a study that uses MD simulations as the main tool to represent a binary system. The MD methodologies of this work will be applied to represent our future studies of menadione derivatives in SC-CO2.

Diffusivity of Cucurbitacin B in water swollen polyethylene oxide-b-polycaprolactone matrices with different PCL/PEO weight ratios

We used isobaric–isothermal molecular dynamics simulation to study the diffusivity of a hydrophobic drug Cucurbitacin B (CuB) in polymer matrices made up of a single polyethylene oxide-b-polycaprolactone (PEO-b-PCL) chain and different numbers of water molecules at body temperature (310K) and ambient pressure (1bar). Four PEO-b-PCL models were used. Three of them had the same total molecular weight of 3750g/mol but different PCL/PEO weight ratios at 0.5, 1 and 2. The remaining model had a total molecular weight of 5000g/mol and a PCL/PEO weight ratio of 1. The data showed that self-diffusion coefficients of CuB decreased with increasing PCL/PEO weight ratio and was insensitive to the water concentration at fixed PCL/PEO weight ratios. The first observation was attributed to a high number of hydrogen bonds formed between the oxygen atoms on CuB and the activated hydrogen atoms on the PCL block as the PCL/PEO weight ratio increased. It was found that degree of swelling and effects of the mobility of the PEO and PCL blocks on the diffusivity of CuB were minor and were overshadowed by the PCL block-CuB hydrogen bonds.

A molecular dynamics simulation of thermodynamic properties of 1, 3, 5-triamino-2, 4, 6-trinitrobenzene under high pressure and high temperature

Equation of states and thermodynamic properties of insensitive high explosive 1, 3, 5-triamino-2, 4, 6-trinitrobenzene (TATB) are investigated by using molecular dynamics simulation, where an all-atom force field for TATB developed by Richard H. Gee and isothermal-isobaric molecular dynamics (NPT-MD) methods are used. Results obtained include thermal expansion coefficient, elastic constants, tensile modulus, and debye frequency under high temperature and high pressure. The volume coefficient of thermal expansion for crystalline TATB is calculated in a temperature range of 200 to 500 K and at atmospheric pressure. The result, 35.910-5 K-1, is in general agreements with the experimental results. Results of elastic constants show that the crystalline TATB is an orthotropic material. The calculated elastic constants decrease with increasing temperature in the range from 0 to 450 K, while increase as the pressure increases from 0 to 50 GPa. And the bulk modulus at 300 K is 11.32 GPa, which is in good agreement with the available experimental results. Results obtained above have been compared with available experimental data, and also discussed in relation to the previous calculations. The above results are better than existing ones gained by others. In addition, the elastic anisotropy becomes lower with increasing temperature or pressure. As the temperature goes up to 400 K, the lattice becomes unstable. The sound speed and Debye frequency are calculated by using the data of elastic constants at different pressures. This provides a theoretical basis to calculate the anisotropic thermal conductivity for crystalline TATB.

Low-mass molecular dynamics simulation for configurational sampling enhancement: More evidence and theoretical explanation

It has been reported recently that classical, isothermal–isobaric molecular dynamics (NTP MD) simulations at a time step of 1.00fs of the standard-mass time (Δt=1.00fssmt) and a temperature of ≤340K using uniformly reduced atomic masses by tenfold offers better configurational sampling than standard-mass NTP MD simulations at the same time step. However, it has long been reported that atomic masses can also be increased to improve configurational sampling because higher atomic masses permit the use of a longer time step. It is worth investigating whether standard-mass NTP MD simulations at Δt=2.00 or 3.16fssmt can offer better or comparable configurational sampling than low-mass NTP MD simulations at Δt=1.00fssmt. This article reports folding simulations of two β-hairpins showing that the configurational sampling efficiency of NTP MD simulations using atomic masses uniformly reduced by tenfold at Δt=1.00fssmt is statistically equivalent to and better than those using standard masses at Δt=3.16 and 2.00fssmt, respectively. The results confirm that, relative to those using standard masses at routine Δt=2.00fssmt, the low-mass NTP MD simulations at Δt=1.00fssmt are a simple and generic technique to enhance configurational sampling at temperatures of ≤340K.

Prediction of self diffusion coefficients of selected solvents in poly(vinyl alcohol) using lattice-free volume theory

The free volume model is probably the most successful model for predicting the diffusivity of small molecules in polymers. However, the experimental procedure for parameterizing the model is not trivial and in fact extremely time consuming. In this work, we propose a much less time consuming approach for the parameterization step. In particular, we carried out isobaric-isothermal molecular dynamics simulations to generate thermodynamic data of a few selected polymer/solvent systems and used the data to parameterize the corresponding Sanchez–Lacombe equation of state (SLEOS). The characteristic parameters of the SLEOS were then used in the parameterization of the lattice free volume (LFV) model so that diffusivity of the solvents in a polymer was then determined. To illustrate the newly proposed approach, we used poly(vinyl alcohol) and water, ethanol and benzene over a concentration range of 1–20 wt% and a temperature range of 270–370 K. We found that the LFV model was much easier to be parametrized in the aforementioned approach and yielded predictions much better than those of the well-known Mackie-Meares model. We also demonstrated that the two adjustable parameters of the LFV model are related to the size of the solvent molecules and their interaction with the polymer.

Ewald summation approach to potential models of aqueous electrolytes involving gaussian charges and induced dipoles: formal and simulation results.

We present a detailed derivation of the complete set of expressions required for the implementation of an Ewald summation approach to handle the long-range electrostatic interactions of polar and ionic model systems involving Gaussian charges and induced dipole moments with a particular application to the isobaric-isothermal molecular dynamics (NPT-MD) simulation of our Gaussian charge polarizable (GCP) water model and its extension to aqueous electrolyte solutions. The set is comprised of the individual components of the potential energy, electrostatic potential, electrostatic field and gradient, electrostatic force, and corresponding virial. Moreover, we show how the derived expressions converge to known point-based electrostatic counterparts when the parameters, defining the Gaussian charge and induced dipole distributions, are extrapolated to their limiting point values. Finally, we test the simulation outcomes from the Ewald implementation against the corresponding reaction-field (RF) approach at three contrasting hydrogen-bonded water environments, including thermodynamic quantities, polarization behavior, and microstructural properties, where the simulated microstructures are compared with the available neutron scattering and X-ray diffraction data.

Low-mass molecular dynamics simulation: A simple and generic technique to enhance configurational sampling

CLN025 is one of the smallest fast-folding proteins. Until now it has not been reported that CLN025 can autonomously fold to its native conformation in a classical, all-atom, and isothermal–isobaric molecular dynamics (MD) simulation. This article reports the autonomous and repeated folding of CLN025 from a fully extended backbone conformation to its native conformation in explicit solvent in multiple 500-ns MD simulations at 277K and 1atm with the first folding event occurring as early as 66.1ns. These simulations were accomplished by using AMBER forcefield derivatives with atomic masses reduced by 10-fold on Apple Mac Pros. By contrast, no folding event was observed when the simulations were repeated using the original AMBER forcefields of FF12SB and FF14SB. The results demonstrate that low-mass MD simulation is a simple and generic technique to enhance configurational sampling. This technique may propel autonomous folding of a wide range of miniature proteins in classical, all-atom, and isothermal–isobaric MD simulations performed on commodity computers—an important step forward in quantitative biology.

Molecular Dynamics Simulation of Dipole Layer Formation at High-k/SiO2 Interfaces

Implementation of high-k/metal gate stack poses a challenge in controlling the threshold voltage (VTH) of MOSFET devices. Recent studies have shown that an electric dipole layer formed at high-k/SiO2 interface is responsible for anomalous VTH shifts. The origin of the dipole layer has been explained by several mechanisms, such as the areal density difference of O atoms [1], electronegativity difference [2], and contact induced gap state [3]. Among these models, the first model proposed by Kita and Toriumi [1] is noteworthy because of its simplicity and potential to be applicable to wide variety of high-k materials. The model states that the interface dipole is formed by the movement of negatively charged O ions from higher oxygen-density side to a lower one.Recently, we performed molecular dynamics (MD) simulations of high-k/SiO2 interfaces and succeeded in reproducing the O atom migration across the Al2O3/SiO2 interface [4]. The O ion moves one-sidedly from Al2O3 side to SiO2 one, but opposite movement never occurs. The simulation result implies that the O ion migration is induced by some drift forces, but not by a simple diffusion due to the O density gradient across the high-k/SiO2. In this paper, we discuss the driving force of the O ion migration across the high-k/SiO2 in terms of the multipole moment around oxide cation.The MD simulation was performed by a commercial simulation package SCIGRESS ME from Fujitsu Ltd. Al2O3/SiO2 interface model was constructed by sandwiching amorphous Al2O3 blocks in between amorphous SiO2 blocks as shown in Fig.1. The hetero-oxide structure was annealed by the isothermal-isobaric MD calculation for 100 ps, thermostated at 1000 K by a velocity scaling with keeping the pressure at atmospheric pressure. The Born-Mayer-Huggins potential is employed in the MD simulation.Figure 2(a) shows a charge density profile across the SiO2/Al2O3 interface. Electric dipole layer appears at the interface, and it is directed from the SiO2 side to Al2O3 side. Figure 2(b) shows the electric potential profile around the interface, which is obtained by solving one-dimensional Poisson’s equation. The built-in potential at SiO2/Al2O3 interface is about 0.5 V, which matches the experimental value of the flat-band voltage shift [1]. Thus the direction and magnitude of the dipole moment in our model agrees with the experimental result. Figure 3 shows the magnified image of the SiO2/Al2O3 interface, in which the O ions originated from Al2O3 are colored by green. It can be clearly seen that the O ion moves one-sidedly from Al2O3 side to SiO2 one.The simulation result indicates that the O ion is driven by some drift forces, but not by a simple diffusion due to the density difference at the interface. It is inferred that the O ions in Al2O3 are attracted to the strong positive charges of Si ions. The positive charges of Si ions must be canceled by the negative charges of O ions in SiO2, but at very close distance, there is an appreciable octupole moment around the Si ion which is located at the center of SiO4 tetrahedron (see Fig.4). On the other hand, there is an hexadecapole moment around the Al ion which located at the center of AlO6octahedron. The electrostatic field induced by the octupole moment around the Si ion is stronger than that of the hexadecapole moment around the Al ion, and thus O ions in the vicinity of the interface can be attracted to Si ions in specific directions. Opposite dipole formation at SiO2/Y2O3interface can also be explained by the difference in the multipole moments around Si and Y ions [4].The multipole moment around an oxide cation is relevant to its electronegativity of the O density of the oxide. Therefore, our “multipole moment induced O migration model” can be regarded as the unified model of the O density [1] model and the electronegativity model [2]. Acknowledgement This work is supported by JST-CREST, and a Grant-in-Aid for Scientific Research (B) from the MEXT Japan.

Molecular dynamics study of the diffusivity of a hydrophobic drug Cucurbitacin B in pseudo-poly(ethylene oxide-b-caprolactone) micelle environments.

Isobaric-isothermal molecular dynamics simulation was used to study the diffusion of a hydrophobic drug Cucurbitacin B (CuB) in pseudomicelle environments consisting of poly(ethylene oxide-b-caprolactone) (PEO-b-PCL) swollen by various amounts of water. Two PEO-b-PCL configurations, linear and branched, with the same total molecular weight were used. For the branched configuration, the block copolymer contained one linear block of PEO with the same molecular weight as that of the PEO block used in the linear configuration but with one end connecting to three PCL blocks with the same chain length, hereafter denoted PEO-b-3PCL. Regardless of the configuration, the simulation results showed that the diffusivity of CuB was insensitive to the water concentration up to ∼8 wt % while that of water decreased with an increasing water concentration. The diffusivity of CuB (10(-8) cm(2)/s) was 3 orders of magnitude lower than that of water (10(-5) cm(2)/s). This is attributed to the fact that CuB relied on the wiggling motion of the block copolymers to diffuse while water molecules diffused via a hopping mechanism. The rates at which CuB and water diffused into PEO-b-PCL were twice those in PEO-b-3PCL because the chain mobility and the degree of swelling are higher and there are fewer intermolecular hydrogen bonds in the case of PEO-b-PCL. The velocity autocorrelation functions of CuB show that the free volume holes formed by PEO-b-3PCL are more rigid than those formed by PEO-b-PCL, making CuB exhibit higher-frequency collision motion in PEO-b-3PCL than in PEO-b-PCL, and the difference in frequency is insensitive to water concentration.

Intercalation of dodecylamine into kaolinite and its layering structure investigated by molecular dynamics simulation

Dodecylamine was successfully intercalated into the layer space of kaolinite by utilizing the methanol treated kaolinite–dimethyl sulfoxide (DMSO) intercalation complex as an intermediate. The basal spacing of kaolinite, measured by X-ray diffraction (XRD), increased from 0.72nm to 4.29nm after the intercalation of dodecylamine. Also, the significant variation observed in the Fourier Transform Infrared Spectroscopy (FTIR) spectra of kaolinite when intercalated with dodecylamine verified the feasibility of intercalation of dodecylamine into kaolinite. Isothermal-isobaric (NPT) molecular dynamics simulation with the use of Dreiding force field was performed to probe into the layering behavior and structure of nanoconfined dodecylamine in the kaolinite gallery. The concentration profiles of the nitrogen atom, methyl group and methylene group of intercalated dodecylamine molecules in the direction perpendicular to the kaolinite basal surface indicated that the alkyl chains within the interlayer space of kaolinite exhibited an obvious layering structure. However, the unified bilayer, pseudo-trilayer, or paraffin-type arrangements of alkyl chains deduced based on their chain length combined with the measured basal spacing of organoclays were not found in this study. The alkyl chains aggregated to a mixture of ordered paraffin-type-like structure and disordered gauche conformation in the middle interlayer space of kaolinite, and some alkyl chains arranged in two bilayer structures, in which one was close to the silica tetrahedron surface, and the other was close to the alumina octahedron surface with their alkyl chains parallel to the kaolinite basal surface.

Simulation of high-density water: Its glass transition for various water models

High-density amorphous water is simulated by use of isothermal-isobaric molecular dynamics at a pressure of 0.3 GPa making use of several water models (SPC/E, TIP3P, TIP4P variants, and TIP5P). Heating/cooling cycles are performed in the temperature range 80-280 K and quantities like density, total energy, and mobility are analysed. Raw data as well as the glass transition temperatures Tg observed in our studies depend on the water model used as well as on the treatment of intramolecular bonds and angles. However, a clear-cut evidence for the occurrence of a glass-to-liquid transition is found in all cases. Thus, all models indicate that high-density amorphous ice found experimentally may be a low-temperature proxy of an ultraviscous high-density liquid.

The effect of urea in the nucleation process of CO2 clathrate hydrates

The role of urea in the promotion and stability of CO2 clathrate hydrates in the context of nucleation was investigated through isothermal–isobaric molecular dynamics simulations. A comparison of structural and dynamic properties was made for aqueous solutions of CO2 interstitial to model montmorillonite surfaces in the presence and absence of urea. The results showed that meta-stable amorphous hydrates associated through proximity interact through cross-relaxation of H-bonds. Urea appears to mediate this effect by functioning as a bridge for thermal fluctuations of H-bond networks between nearby CO2 hydrates. The implications have significant bearing in the modification of solution properties for the enhancement of clathrate hydrate formation in geologic and aquatic sediments through the control and stabilization of nucleation using organic matter.

Force field comparison and thermodynamic property calculation of supercritical CO2 and CH4 using molecular dynamics simulations

Thermodynamic properties of carbon dioxide and methane have been calculated under supercritical conditions up to 900K and 100MPa using isothermal-isobaric molecular dynamics simulations and the multistate Bennett acceptance ratio (MBAR) technique. Seven different carbon dioxide force fields (two single-site models, three rigid three-site models, and two fully flexible three-site models) were considered for preliminary density calculation. Those showing better accuracy when compared to experimental results were used to calculate the volume expansivity, isothermal compressibility, isobaric and isochoric heat capacities, Joule–Thomson coefficient, and speed of sound. The same properties were also calculated for methane using two different single-site models.The results show that force fields originally parameterized and optimized to reproduce vapor–liquid coexistence curves may be able to give accurate predictions of other thermodynamic properties in an extended temperature and pressure range. The results obtained with molecular simulations are generally more accurate than predictions with the Peng–Robinson equation of state, especially near critical conditions and at high pressures. Furthermore, the MBAR technique is successfully applied to improve the accuracy of results, decrease calculation uncertainties and reduce the number of simulations required to provide reliable property predictions over a range of temperatures and pressures. Recommendations are made as to which force fields are most accurate for the set of properties computed here.

CO32–Mobility in Carbonate Apatite As Revealed by Density Functional Modeling

Carbonate apatite is a material of the utmost importance as it represents the inorganic fraction of biological hard tissues in bones and teeth. Here we study the static and dynamic features of CO32– ion in the apatitic channel of carbonate apatite (A-type substitution), by applying both static and dynamic quantum mechanical calculations based on density functional methods with B3LYP-D* and PBE functionals. The static calculations reveal a number of almost energetically equivalent carbonate configurations in the channel, leading to cell parameters compatible with the P3 space group assigned by the experimental X-ray structure determination. Ab initio isothermal–isobaric molecular dynamics simulations provide insights on the CO32– mobility, showing that at the temperature of the experimental structural determination the CO32– moiety undergoes a dynamic disorder, as the carbonate group is almost free to move within the apatitic channel enhancing its exchangeability with other anions.

Simulated defect growth avalanches during deformation of nanocrystalline copper

In this work we introduce a method to capture the proliferation of material defects that carry inelastic deformation, in microstructures simulated through isobaric–isothermal molecular dynamics. Based on the premise that inelastic dissipation is accompanied by a local temperature rise, our method involves analyzing the response of a chain of Nosé–Hoover thermostats that are coupled to the atomic velocities, while the microstructure deforms under the influence of a ramped external stress. We report results obtained from the uniaxial deformation of two nanocrystalline copper microstructures and show that our analysis allows the dissipative signal of a variety of inelastic events to be effectively unified via an ‘avalanche’ of dissipation. Based on this avalanche, we quantitatively compare dissipation for inelastic deformation under tension vs. compression, observing a significant tension–compression asymmetry in this regard. It is concluded that the present method is useful for discerning critical points that correspond to collective yield and inelastic flow.

High pressure miscibility predictions of polyethylene in hexane solutions based on molecular dynamics

Models that describe miscibility of polyethylene in hydrocarbon solvents at high pressures are of on-going interest in fundamental polymer physics and applied polymer processing. The present study aims to characterize the pressure dependence of the solubility of polyethylene (PE) in hexane using an atomistic-level simulation technique to avoid the need for expensive and difficult to obtain experimental data. To achieve this, isobaric–isothermal molecular dynamics (NPT-MD) simulations based upon a well-established force field (OPLS-AA) are utilized to predict the pressure dependence of Hildebrand’s solubility parameter of high-density polyethylene (HDPE) and hexane at high pressure. The NPT simulations also capture molar volume data computed at high temperature (425K) and high pressures ranging from 100 to 3000bar. Further, internal pressures are estimated at high pressures and it is shown that for PE internal pressure is not identical to cohesive energy density (CED). However for PE the ratio of these two quantities tends to unity with increasing pressure. Subsequently, the Flory–Huggins binary interaction parameter is predicted from the knowledge of pressure dependence of solubility parameters and molar volumes. It is demonstrated that the computed binary interaction parameter decreases upon increasing the pressure indicating that the miscibility of the PE/hexane system improves by raising the pressure. This conclusion is in agreement with the solution polymerization process for producing PE where pressure-induced phase separation (PIPS) is applied to separate the polymer product from the polyolefin solution. Exclusion of electrostatic potentials in the molecular mechanics model results in larger interaction parameters while the monotonically decreasing trend remains intact in both molecular mechanics models with and without electrostatic forces. In addition, it has been found that there is a pressure limit beyond which the binary interaction parameter demonstrates less sensitivity to pressure indicating that PE miscibility is not further affected by pressure changes. Based upon the pressure dependence of the interaction parameter the negative contribution of volume change on mixing is predicted where the change in volume upon mixing decays with increasing pressure. Moreover, it is shown that the increase in system pressure increases the chemical potential factor of the phase stability condition indicating that at higher pressures this term tends to stabilize the polymer–solvent system. It has also been revealed that the chemical potential factor estimated by the molecular mechanics model, incorporating the atomic partial charges, is qualitatively more consistent with the miscibility predictions from phase diagrams. The presented results contribute to the fundamental understanding of PIPS, an important demixing process poorly understood when compared to thermally-induced phase separation.