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HIV-1 protease (HIV-1-pr) plays an important role in viral replication and maturation, making it one of the most attractive targets for anti-retroviral therapy. To design new effective inhibitors able to combat drug resistance in mutant HIV-1-pr variants, it is essential to gain further understanding about the mechanisms by which the recently proposed inhibitors deactivate the mutant HIV-1-pr variants. In the present work, we explored the interactions between two P2-ligands (DRV, and one new derivative, 4UY) with wild type (WT) and two multiple mutant HIV-1-pr variants (p20 and p51) with all atom molecular dynamics (MD) simulations, binding free energy calculations, and principal component analysis (PCA). The trajectories of MD simulations show that both 4UY and DRV primarily bind with the active sites, flap and 80s loop regions of HIV-1-pr variants through either hydrogen bonds or hydrophobic interactions. More hydrogen bonds and hydrophobic interactions were located for 4UY/HIV-1-pr complexes than for DRV/HIV-1-pr counterparts. More importantly, 4UY was found to have an extra hydrogen bond with the backbone of Gly48' in the flap region of the HIV-1-prs. The flap tip-tip distance (I50–I50') and flap tip-active site distance (I50-D25 and I50′-D25') indicate that the flaps turn more closed in 4UY bound HIV-1-prs than DRV bound ones, and the former also have more compact hydrophobic cavities than the latter. Further, the vector projections from PCA indicate that 4UY/DRV inhibitor binding projects the closing of flap in HIV-1-pr variants. In line with the above trajectory analysis, the thermodynamics calculation with MM-PBSA method suggests much stronger binding affinity for 4UY/HIV-1-pr than DRV/HIV-1-pr by 4.3–6.4 kcal/mol. Although p20 and p51 also induce weaker binding due to multiple mutants for 4UY inhibitor by 1.9–1.8 kcal/mol, their bindings to the new P2 ligand (4UY) are indeed significantly enhanced as compared to DRV. The thermodynamic components responsible for the binding differences and the contribution from key residues to the binding were also discussed in detail. Image 1 • 4UY has more hydrogen bonds and hydrophobic contacts with HIV-1-prs , bringing about smaller hydrophobic cavity than in the case of DRV. • Quantitatively, 4UY binds stronger to HIV-1-prs by 4.3-6.4 kcal/mol than DRV. • The thermodynamic components responsible for the binding differences and the contribution from key residues to the binding were also discussed. [ABSTRACT FROM AUTHOR]

Reinforcing cementitious composites with nanomaterials is an effective way to reduce porosity and enhance thermal conductivity (TC). In this study, the TCs of cementitious composites were predicted using an innovative theoretical framework combining numerical simulations (molecular dynamics) and theoretical analyses (homogenization theory and effective medium theory). The effects of thermal and geometric parameters upon the TC were investigated. Graphene and graphene oxide were selected as representative nanomaterials to estimate the TC, owing to excellent heat transfer property. According to the theoretical framework, two evaluation indicators were firstly provided to evaluate the reinforcing effect of nanomaterials upon the TC. This study provides theoretical support and specifications for practical experiments and engineering applications. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract As a new excellent semiconductor material, black phosphorus (BP) has wide application in nanodevices. Its stability can be improved by reducing edge unsaturated atoms. In this study, we investigated the self-assembly of a BP nanotube (BPNT) from a parallelogram ribbon driven by a C 60 -encapsulated CNT (i.e., peapod). Effects of CNT radius, number of fullerenes, and temperature on the self-assembly results were evaluated by molecular dynamics simulations. Briefly, a BPNT can be formed from the same BP ribbon on a narrower CNT with more fullerenes at higher temperature. This will benefit potential application of the present method in fabrication of BPNTs. [ABSTRACT FROM AUTHOR]

Inhibitors of HIV-1 protease (HIV-1-pr) generally only bind to the active site of the protease. However, for some mutants such as V32I and M46L the TMC114 can bind not only to the active cavity but also to the groove of the flexible flaps. Although the second binding site suggests the higher efficiency of the drug against HIV-1-pr, the drug resistance in HIV-1-pr due to mutations cannot be ignored, which prompts us to investigate the molecular mechanisms of drug resistance and behavior of double bound TMC114 (2T) to HIV-1-pr. The conformational dynamics of HIV-1-pr and the binding of TMC114 to the WT, V32I and M46L mutants were investigated with all-atom molecular dynamic (MD) simulation. The 20 ns MD simulation shows many fascinating effects of the inhibitor binding to the WT and mutant proteases. MM-PBSA calculations explain the binding free energies unfavorable for the M46L and V32I mutants as compared to the WT. For the single binding (1T) the less binding affinity can be attributed to the entropic loss for both V32I-1T and M46L-1T. Although the second binding of TMC114 with flap does increase binding energy for the mutants (V32I-2T and M46L-2T), the considerable entropy loss results in the lower binding Gibbs free energies. Thus, binding of TMC114 in the flap region does not help much in the total gain in binding affinity of the system, which was verified from this study and thereby validating experiments. [ABSTRACT FROM AUTHOR]

Abstract: Most of the currently treated HIV-1 protease (HIV-PR) inhibitors have been prone to suffer from the mutations associated drug resistance. Therefore, it is necessary to search for potent alternatives against the drug resistance. In the current study we have tested the single-walled carbon nanotube (SWCNT) as an inhibitor in wild type (WT) as well as in three primary mutants (I50VPR, V82APR and I84VPR) of the HIV-1-PR through docking the SWCNT in the active site region, and then performed all-atom MD simulations for the complexes. The conformational dynamics of HIV-PR with a 20ns trajectory reveals that the SWCNT can effectively bind to the HIV-1-PR active site and regulate the flap dynamics such as maintaining the flap-flap closed. To gain an insight into the binding affinity, we also performed the MM-PBSA based binding free energy calculations for the four HIV-PR/SWCNT complexes. It was observed that, although the binding between the SWCNT and the HIV-PR decreases due to the mutations, the SWCNTs bind to the HIV-PRs 3–5 folds stronger than the most potent HIV-1-PR inhibitor, TMC114. Remarkably, the significant interactions with binding energy higher than 1kcal/mol focus on the flap and active regions, which favors closing flap-flap and deactivating the active residues of the HIV-PR. The flap dynamics and binding strength information for HIV-PR and SWCNTs can help design SWCNT-based HIV-1-PR inhibitors. [Copyright &y& Elsevier]

In the present work, the binding of inhibitor TMC114(darunavir)to wild-type (WT), single (I50V) as well as double (I50L/A71V) mutantHIV-proteases (HIV-pr) was investigated with all-atom molecular dynamics(MD) simulations as well as molecular mechanic-Poisson–Boltzmannsurface area (MM-PBSA) calculation. For both the apo and complexedHIV-pr, many intriguing effects due to double mutant, I50L/A71V, areobserved. For example, the flap–flap distance and the distancefrom the active site to the flap residues in the apo I50L/A71V-HIV-prare smaller than those of WT- and I50V–HIV-pr, probably makingthe active site smaller in volume and closer movement of flaps. Forthe complexed HIV-pr with TMC114, the double mutant I50L/A71V showsa less curling of the flap tips and less flexibility than WT and thesingle mutant I50V. As for the other previous studies, the presentresults also show that the single mutant I50V decreases the bindingaffinity of I50V–HIV-pr to TMC, resulting in a drug resistance;whereas the double mutant I50L/A71V increases the binding affinity,and as a result of the stronger binding, the I50L/A71V may be welladapted by the TMC114. The energy decomposition analysis suggeststhat the increase of the binding for the double mutant I50L/A71V–HIV-prcan be mainly attributed to the increase in electrostatic energy by−5.52 kacl/mol and van der Waals by −0.42 kcal/mol,which are canceled out in part by the increase of polar solvationenergy of 1.99 kcal/mol. The I50L/A71V mutant directly increases thebinding affinity by approximately −0.88 (Ile50 to Leu50) and−0.90 (Ile50′ to Leu50′) kcal/mol, accounting45% for the total gain of the binding affinity. Besides the directeffects from the residues Leu50 and Leu50′, the residue Gly49′increases the binding affinity of I50L/A71V–HIV-pr to the inhibitorby −0.74 kcal/mol, to which the electrostatic interaction ofLeu50''s backbone contributes by −1.23 kcal/mol. Another tworesidues Ile84 and Ile47′ also increase the binding affinityby −0.22 and −0.29 kcal/mol, respectively, which canbe mainly attributed to van der Waals terms (ΔTvdw= −0.21 and −0.39 kcal/mol). [ABSTRACT FROM AUTHOR]

• High temperature reduces the adhesion between asphalt and concrete. • As the new bond is generated, the adhesion of asphaltene-phenol is the strongest. • Aging reduces the adhesion of molecules and has more impact at high temperatures. In this paper, reactive molecular dynamics is used to investigate the adhesion between asphalt molecules and aggregates, and explore the mechanism of action between asphalt and aggregates. Different asphalt molecules, system temperatures and aging of asphalt are considered. Through numerical simulation, it was found that there are physical (van der Waals force) and chemical interactions between the aggregates and the asphaltene molecules containing hydrogen atoms. The new bond is generated through the chemical reaction, which provides strong bonding force to enhance the adhesion of the interface. Other types of molecules and aggregates are only combined through physical attraction, and the bonding force is weak. In addition, the aging of the asphalt causes the loss of hydrogen atoms, so the adhesion between the asphalt and the aggregate is weakened. In summary, numerical simulation results provided a reference for the research and production of asphalt materials with better adhesion properties. [ABSTRACT FROM AUTHOR]

• Self-assembly of a black phosphorus (BP) ribbon on CNTs with different shapes were studied. • Relative position of CNT and BP ribbon influences self-assembly result. • A perfect BP nanotube can be obtained from the ribbon on a shorter CNT at higher temperature. • Mechanism was revealed of the successful formation of a BP nanotube from the ribbon. To form a black phosphorus (BP) nanotube by self-assembly of a parallelogram BP ribbon, a carbon nanotube is adopted to trigger the self-assembly process. Both the length and position of a CNT influence the van der Waals force on the BP ribbon. In this study, molecular dynamics simulations were adopted to reveal the effects of the two geometrical factors on the self-assembly process. The results show that the BP ribbon can form into a nanotube on shorter CNTs at higher temperature below 50 K. The mechanism is that at the CNT ends, non-uniform attraction to the BP ribbon is essential to fold of the ribbon and alignment of the two oblique edges. The misalignment of their mass centers of the two components will benefit a successful self-assembly of a BP nanotube. The new understanding provides a reference for the production of BPNTs. [ABSTRACT FROM AUTHOR]

It is difficult to obtain a nanotube from phosphorus with a 3sp2 electron configuration by chemical synthesis. However, a physical fabrication approach, such as self-assembly, is worth trying. In an experiment, when using a carbon nanotube (CNT) to trigger self-assembly of a black phosphorus (BP) ribbon, the final configuration of the BP component may be sensitive to the initial relative position of the CNT to the BP ribbon. For instance, using the same CNT with different initial relative positions to the BP ribbon, the BP ribbon may finally become a nanotube, or a scroll, or just wind upon the CNT, or escape from the CNT, etc. In this study, the sensitivity is investigated using molecular dynamics simulations. Numerical results illustrate some essentials for potential fabrication of a BP nanotube from ribbon. [ABSTRACT FROM AUTHOR]

In the present work, the molecular dynamics study method has been utilised to investigate the effects of pressure on the volatilisation of pure Bi nanoparticles and Bi–Fe core–shell nanoparticles during continuous heating. Computational total energy curves between 300 and 2000 K are used to explore the structural changes of nanoparticles under different pressures. On the other hand, the radial distribution function is examined to determine the structural evolution of a system. The calculated root mean square displacement curves under pressures of 0–5 GPa between 300 and 2000 K are employed to explore the diffusion of Bi element and the calculated volatilisation rate of Bi element is used to quantitatively obtain the volatilisation characteristics. The volatilisation patterns of pure Bi nanoparticles and Bi–Fe core–shell nanoparticles are different under different temperatures and pressures. The results show that the volatilisation of Bi element is increasing during the heating from 300 to 2000 K, and the volatilisation decreases with the increase of pressure. Furthermore, the Fe shell can effectively decrease the volatilisation of the Bi element. [ABSTRACT FROM AUTHOR]

Abstract: Density functional theory and classical molecular dynamics simulations permit us to elucidate details of ionic and molecular transport useful for the design of polymer electrolyte membranes. We consider two systems of current interest: (a) ionic transport in polyethylene-oxide compared to that in a polyphosphazene membrane targeted to be a good ionic carrier but a bad water carrier and (b) transport of oxygen and protons through hydrated nafion in the vicinity of a catalyst phase. It is shown that in polyphosphazene membranes, nitrogen atoms interact more strongly with lithium ions than ether oxygens do. As a result of the different complexation of Li+ with the polymer sites, Li+ has a much higher diffusion coefficient in polyphosphazene than in polyethylene oxide electrolyte membranes, with the consequent relevance to lithium–water battery technology. For the hydrated membrane/catalyst interface, our simulations show that the Nafion membrane used in low-temperature fuel cells interacts strongly with the catalytic metal nanoparticles directing the side chain towards the catalyst surface. Results at various degrees of hydration of the membrane illustrate the formation of water clusters surrounding the polymer hydrophilic sites, and reveal how the connectivity of these clusters may determine the transport mechanism of protons and molecular species. [Copyright &y& Elsevier]

Abstract: A novel hybrid density functional theory, MPWB1K, was firstly employed to investigate static adsorptions of a nifedipine on a (10,10) type of single-walled carbon nanotube (SWCNT), which was modeled by C200H40 and C280, respectively. For both SWCNT models the internal adsorption is more stable than the external adsorption in a range of 5.3–7.8kcal/mol, which indicates that a nifedipine has a preference to internally adsorb on the (10,10) SWCNT. Molecular dynamic simulations were then used to predict the dynamic behaviors of a nifedipine and the (10,10) SWCNT system in both gas phase and aqueous solution. The classical MD simulations show that for both cases a nifedipine could spontaneously encapsulate into the SWCNT and migrate in a surprising oscillation behavior inside the SWCNT; however, both phenomena are significantly delayed in the presence of water molecules. The present study suggests that the nanotube network may be used as an efficient tool for transporting this kind of calcium channel antagonists. [Copyright &y& Elsevier]