Peng Xiu

Destructive extraction of phospholipids from Escherichia coli membranes by graphene nanosheets

Understanding how nanomaterials interact with cell membranes is related to how they cause cytotoxicity and is therefore critical for designing safer biomedical applications. Recently, graphene (a two-dimensional nanomaterial) was shown to have antibacterial activity on Escherichia coli, but its underlying molecular mechanisms remain unknown. Here we show experimentally and theoretically that pristine graphene and graphene oxide nanosheets can induce the degradation of the inner and outer cell membranes of Escherichia coli, and reduce their viability. Transmission electron microscopy shows three rough stages, and molecular dynamics simulations reveal the atomic details of the process. Graphene nanosheets can penetrate into and extract large amounts of phospholipids from the cell membranes because of the strong dispersion interactions between graphene and lipid molecules. This destructive extraction offers a novel mechanism for the molecular basis of graphenes cytotoxicity and antibacterial activity.

Water-mediated signal multiplication with Y-shaped carbon nanotubes

Molecular scale signal conversion and multiplication is of particular importance in many physical and biological applications, such as molecular switches, nano-gates, biosensors, and various neural systems. Unfortunately, little is currently known regarding the signal processing at the molecular level, partly due to the significant noises arising from the thermal fluctuations and interferences between branch signals. Here, we use molecular dynamics simulations to show that a signal at the single-electron level can be converted and multiplied into 2 or more signals by water chains confined in a narrow Y-shaped nanochannel. This remarkable transduction capability of molecular signal by Y-shaped nanochannel is found to be attributable to the surprisingly strong dipole-induced ordering of such water chains, such that the concerted water orientations in the 2 branches of the Y-shaped nanotubes can be modulated by the water orientation in the main channel. The response to the switching of the charge signal is very rapid, from a few nanoseconds to a few hundred nanoseconds. Furthermore, simulations with various water models, including TIP3P, TIP4P, and SPC/E, show that the transduction capability of the Y-shaped carbon nanotubes is very robust at room temperature, with the interference between branch signals negligible.

Amino acid analogues bind to carbon nanotube via π-π interactions: Comparison of molecular mechanical and quantum mechanical calculations

Understanding the interaction between carbon nanotubes (CNTs) and biomolecules is essential to the CNT-based nanotechnology and biotechnology. Some recent experiments have suggested that the π-π stacking interactions between proteins aromatic residues and CNTs might play a key role in their binding, which raises interest in large scale modeling of protein-CNT complexes and associated π-π interactions at atomic detail. However, there is concern on the accuracy of classical fixed-charge molecular force fields due to their classical treatments and lack of polarizability. Here, we study the binding of three aromatic residue analogues (mimicking phenylalanine, tyrosine, and tryptophan) and benzene to a single-walled CNT, and compare the molecular mechanical (MM) calculations using three popular fixed-charge force fields (OPLSAA, AMBER, and CHARMM), with quantum mechanical (QM) calculations using the density-functional tight-binding method with the inclusion of dispersion correction (DFTB-D). Two typical configurations commonly found in π-π interactions are used, one with the aromatic rings parallel to the CNT surface (flat), and the other perpendicular (edge). Our calculations reveal that compared to the QM results the MM approaches can appropriately reproduce the strength of π-π interactions for both configurations, and more importantly, the energy difference between them, indicating that the various contributions to π-π interactions have been implicitly included in the van der Waals parameters of the standard MM force fields. Meanwhile, these MM models are less accurate in predicting the exact structural binding patterns (matching surface), meaning there are still rooms to be improved. In addition, we have provided a comprehensive and reliable QM picture for the π-π interactions of aromatic molecules with CNTs in gas phase, which might be used as a benchmark for future force field developments.

Manipulating biomolecules with aqueous liquids confined within single-walled nanotubes.

Confinement of molecules inside nanoscale pores has become an important method for exploiting new dynamics not happening in bulk systems and for fabricating novel structures. Molecules that are encapsulated in nanopores are difficult to control with respect to their position and activity. On the basis of molecular dynamics simulations, we have achieved controllable manipulation, both in space and time, of biomolecules with aqueous liquids inside a single-walled nanotube by using an external charge or a group of external charges. The remarkable manipulation abilities are attributed to the single-walled structure of the nanotube that the electrostatic interactions of charges inside and outside the single-walled nanotube are strong enough, and the charge-induced dipole-orientation ordering of water confined in the nanochannel so that water has a strong interaction with the external charge. These designs are expected to serve as lab-in-nanotube for the interactions and chemical reactions of molecules especially biomolecules, and have wide applications in nanotechnology and biotechnology.

Critical Dipole Length for the Wetting Transition Due to Collective Water-dipoles Interactions

The wetting behavior of water on the solid surfaces is fundamental to various physical, chemical and biological processes. Conventionally, the surface with charges or charge dipoles is hydrophilic, whereas the non-polar surface is hydrophobic though some exceptions were recently reported. Using molecular dynamics simulations, we show that there is a critical length of the charge dipoles on the solid surface. The solid surface still exhibited hydrophobic behavior when the dipole length was less than the critical value, indicating that the water molecules on the solid surface seemed not “feel” attractive interactions from the charge dipoles on the solid surface. Those unexpected observations result from the collective interactions between the water molecules and charge dipoles on the solid surface, where the steric exclusion effect between water molecules greatly reduces the water-dipole interactions. Remarkably, the steric exclusion effect is also important for surfaces with charge dipole lengths greater than this critical length.

Coherent Microscopic Picture for Urea-Induced Denaturation of Proteins

In a previous study, we explored the mechanism of urea-induced denaturation of proteins by performing molecular dynamics (MD) simulations of hen lysozyme in 8 M urea and supported the direct interaction mechanism whereby urea denatures protein via dispersion interaction (Hua, L.; Zhou, R. H.; Thirumalai, D.; Berne, B. J. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 16928). Here we perform large scale MD simulations of five representative protein/peptide systems in aqueous urea to investigate if the above mechanism is common to other proteins. In all cases, accumulations of urea around proteins/peptide are observed, suggesting that urea denatures proteins by directly attacking protein backbones and side chains rather than indirectly disrupting water structure as a water breaker. Consistent with our previous case study of lysozyme, the current energetic analyses with five protein/peptide systems reveal that ureas preferential binding to proteins mainly comes from ureas stronger dispersion interactions with proteins than with bulk solution, whereas the electrostatic (hydrogen-bonded) interactions only play a relatively minor (even negative) role during this denaturation process. Furthermore, the simulations of the peptide system at different urea concentrations (8 and 4.5 M), and with different force fields (CHARMM and OPLSAA) suggest that the above mechanism is robust, independent of the urea concentration and force field used. Last, we emphasize the importance of periodic boundary conditions in pairwise energetic analyses. This article provides a comprehensive study on the physical mechanism of urea-induced protein denaturation and suggests that the dispersion-interaction-driven mechanism should be general.

Alcohol-induced drying of carbon nanotubes and its implications for alcohol/water separation: A molecular dynamics study

Alcohols are important products in chemical industry, but separating them from their aqueous solutions is very difficult due to the hydrophilic nature of alcohols. Based on molecular dynamics simulations, we observe a striking nanoscale drying phenomenon and suggest an energy-saving and efficient approach toward alcohol∕water separation by using single-walled carbon nanotubes (SWNTs). We use various common linear alcohols including C1-C6 1-alcohols and glycerol for demonstration (the phenol is also used as comparison). Our simulations show that when SWNTs are immersed in aqueous alcohols solutions, although the alcohols concentration is low (1 M), all kinds of alcohols can induce dehydration (drying) of nanotubes and accumulate inside wide [(13, 13)] and narrow [(6, 6) or (7, 7)] SWNTs. In particular, most kinds of alcohols inside the narrow SWNTs form nearly uniform 1D molecular wires. Detailed energetic analyses reveal that the preferential adsorption of alcohols over water inside nanotubes is attributed to the stronger dispersion interactions of alcohols with SWNTs than water. Interestingly, we find that for the wide SWNT, the selectivity for 1-alcohols increases with the number of alcohols carbon atoms (Ncarbon) and exhibits an exponential law with respect to Ncarbon for C1-C5 1-alcohols; for narrow SWNTs, the selectivity for 1-alcohols is very high for methanol, ethanol, and propanol, and reaches a maximum when Ncarbon = 3. The underlying physical mechanisms and the implications of these observations for alcohol∕water separation are discussed. Our findings provide the possibility for efficient dehydration of aqueous alcohols (and other hydrophilic organic molecules) by using SWNT bundles∕membranes.

Dewetting transitions in the self-assembly of two amyloidogenic β-sheets and the importance of matching surfaces.

We use molecular dynamics simulations to investigate the water-mediated self-assembly of two amyloidogenic β-sheets of hIAPP(22-27) peptides (NFGAIL). The initial configurations of β-sheet pairs are packed with two different modes, forming a tube-like nanoscale channel and a slab-like 2-D confinement, respectively. For both packing modes, we observe strong water drying transitions occurring in the intersheet region with high occurrence possibilities, suggesting that the dewetting transition-induced collapse may play an important role in promoting the amyloid fibrils formation. However, contrary to general dewetting theory prediction, the slab-like confinement (2-D) shows stronger dewetting phenomenon than the tube-like channel (1-D). This unexpected observation is attributed to the different surface roughness caused by different packing modes. Furthermore, we demonstrated the profound influence of internal surface topology of β-sheet pairs on the dewetting phenomenon through an in silico mutagenesis study. The present study highlights the important role of packing modes (i.e., surface roughness) in the assembly process of β-sheets, which improves our understanding toward the molecular mechanism of the amyloid fibrils formation. In addition, our study also suggests a potential route to regulate controllably the self-assembly process of β-sheets through mutations, which may have future applications in nanotechnology and biotechnology.

Kinetics of water filling the hydrophobic channels of narrow carbon nanotubes studied by molecular dynamics simulations.

The kinetics of water filling narrow single-walled carbon nanotubes was studied using molecular dynamics simulations. The time required to fully fill a nanotube was linear with respect to the tube length. We observed that water molecules could enter into nanotubes of different lengths, either from one end or from both ends. The probability of having a nanotube filled completely from both ends increased exponentially with the tube length. For short tubes, filling usually proceeded from only one end. For long tubes, filling generally proceeded from both tube ends over three stages, i.e., filling from one end, filling from both ends, and filling from both ends with the dipole reorientation of water molecules to give a concerted ordering within the fully filled tube. The water molecules in the partially filled nanotube were hydrogen bonded similarly to those in the fully filled nanotube. Simulations for the reference Lennard-Jones fluid without hydrogen bonds were also performed and showed that the filling behavior of water molecules can be attributed to strong intermolecular hydrogen bonding.

Enantiomerization Mechanism of Thalidomide and the Role of Water and Hydroxide Ions

The significance of the molecular chirality of drugs has been widely recognized due to the thalidomide tragedy. Most of the new drugs reaching the market today are single enantiomers, rather than racemic mixtures. However, many optically pure drugs, including thalidomide, undergo enantiomerization in vivo, thus negating the single enantiomers benefits or inducing unexpected effects. A detailed atomic level understanding of chiral conversion, which is still largely lacking, is thus critical for drug development. Herein, we use first-principle density function theory (DFT) to explore the mechanism of enantiomerization of thalidomide. We have identified the two most plausible interconversion pathways for isolated thalidomide: 1)u2005proton transfer from the chiral carbon center to an adjacent carbonyl oxygen atom, followed by isomerization and rotation of the glutarimide ring (before the proton hops back to the chiral carbon atom); and 2)u2005a pathway that is the same as 1, but with the isomerization of the glutarimide ring occurring ahead of the initial proton transfer reaction. There are two remarkable energy barriers, 73.29 and 23.59u2005kcalu2009mol(-1), corresponding to the proton transfer and the rotation of the glutarimide ring, respectively. Furthermore, we found that water effectively catalyzes the interconversion by facilitating the proton transfer with the highest energy barrier falling to approximately 30u2005kcalu2009mol(-1), which, to our knowledge, is the first time that this important role of water in chiral conversion has been demonstrated. Finally, we show that the hydroxide ion can further lower the enantiomerization energy barrier to approximately 24u2005kcalu2009mol(-1) by facilitating proton abstraction, which agrees well with recent experimental data under basic conditions. Our current findings highlight the importance of water and hydroxide ions in the enantiomerization of thalidomide and also provide new insights into the mechanism of enantiomerization at an atomic level.