Effect of flexibility on hydrophobic behavior of nanotube water channels

Carbon nanotubes can serve as simple nonpolar water channels. Here we report computer simulations exploring the relationship between the mechanical properties of such channels and their interaction with water. We show that on one hand, increasing the flexibility of the carbon nanotubes increases their apparent hydrophobic character, while on the other hand the presence of water inside the channel makes them more resistant to radial collapse. We quantify the effect of increasing flexibility on the hydrophobicity of the nanotube water channel. We also show that flexibility impedes water transport across the nanotube channel by increasing the free-energy barriers to such motion. Conversely, the presence of water inside the nanotube is shown to affect the energetics of radial collapse in a water nanotube, an ostensibly mechanical property. We quantify the magnitude of the effect and show that it arises from the formation of energetically favorable low-dimensional water structures inside the nanotube such as one-dimensional wires and two-dimensional sheets.     

Strong correlations and Fickian water diffusion in narrow carbon nanotubes

The authors have used atomistic molecular dynamics (MD) simulations to study the structure and dynamics of water molecules inside an open ended carbon nanotube placed in a bath of water molecules. The size of the nanotube allows only a single file of water molecules inside the nanotube. The water molecules inside the nanotube show solidlike ordering at room temperature, which they quantify by calculating the pair correlation function. It is shown that even for the longest observation times, the mode of diffusion of the water molecules inside the nanotube is Fickian and not subdiffusive. They also propose a one-dimensional random walk model for the diffusion of the water molecules inside the nanotube. They find good agreement between the mean-square displacements calculated from the random walk model and from MD simulations, thereby confirming that the water molecules undergo normal mode diffusion inside the nanotube. They attribute this behavior to strong positional correlations that cause all the water molecules inside the nanotube to move collectively as a single object. The average residence time of the water molecules inside the nanotube is shown to scale quadratically with the nanotube length.     

Confinement induced conformational changes in n-alkanes sequestered within a narrow carbon nanotube

While alkanes in solution exhibit predominantly extended conformations, nanoscale confinement of these chains within protein binding sites and synthetic receptors can significantly alter the conformer distribution. As a simple model for the effect of confinement on the conformation, we report molecular simulations of n-alkanes absorbed from a bulk solvent into narrow carbon nanotubes. We observe that confinement of butane, hexane, and tetracosane induces a trans to gauche conformational redistribution. Moreover, confined hexane and tetracosane exhibit cooperative interactions between neighboring dihedral angles, which promote a helical gauche conformation for the portions of the chain within the nanotube. Hexane absorbed into the nanotube from water or benzene exhibits essentially the same conformation regardless of the bulk solvent. The PMF between the nanotube and hexane along the central nanotube axis finds that nanotube absorption is favorable from aqueous solution but neutral from benzene. The interaction between hexane and the nanotube in water is dominated by the direct interaction between the alkane and the nanotube and weakly opposed by indirect water-mediated forces. In benzene, however, the direct alkane/nanotube interaction is effectively balanced by the indirect benzene-mediated interaction. Our simulations in water stand in difference to standard interpretations of the hydrophobic effect, which posit that the attraction between non-polar species in water is driven by their mutual insolubility.     

What is the time scale for α-helix nucleation?

Helix formation is an elementary process in protein folding, influencing both the rate and mechanism of the global folding reaction. Yet, because helix formation is less cooperative than protein folding, the kinetics are often multiexponential, and the observed relaxation times are not straightforwardly related to the microscopic rates for helix nucleation and elongation. Recent ultrafast spectroscopic measurements on the peptide Ac-WAAAH(+)-NH(2) were best fit by two relaxation modes on the ～0.1-1 ns time scale, (1) apparently much faster than had previously been experimentally inferred for helix nucleation. Here, we use replica-exchange molecular dynamics simulations with an optimized all-atom protein force field (Amber ff03w) and an accurate water model (TIP4P/2005) to study the kinetics of helix formation in this peptide. We calculate temperature-dependent microscopic rate coefficients from the simulations by treating the dynamics between helical states as a Markov process using a recently developed formalism. The fluorescence relaxation curves obtained from simulated temperature jumps are in excellent agreement with the experimentally determined results. We find that the kinetics are multiphasic but can be approximated well by a double-exponential function. The major processes contributing to the relaxation are the shrinking of helical states at the C-terminal end and a faster re-equilibration among coil states. Despite the fast observed relaxation, the helix nucleation time is estimated from our model to be 20-70 ns at 300 K, with a dependence on temperature well described by Arrhenius kinetics.     

Analysis of the structural and dynamic properties of human N-terminal domain of apolipoprotein E by molecular dynamics simulations

Whereas the lipid-free N-terminal domain of apolipoprotein E (apoE-NT) adopts a four-helix bundle, the lipid-bound form is believed to undergo a large conformational change likely to be characterized by the opening of the bundle. ApoE-NT in a water/alcohol mixture was also shown to experience conformational changes exhibiting similarities with those induced upon lipid binding. The structure and dynamics of apoE-NT have been here investigated by analyzing 40 ns and 60 ns molecular dynamics simulations performed in water and in a water/propanol mixture, respectively. The overall structural properties show alterations of the tertiary structure of apoE-NT in the water/alcohol system in agreement with those observed experimentally. In contrast, in the water simulation, the sampled conformations remain closer to the crystal structure that served as a starting point for both simulations. Interestingly, several propanol molecules are seen to penetrate two hydrophobic regions of the bundle interior. One of these regions is enclosed in part by the short helix (H1') connecting helices 1 and 2 of the bundle which has been experimentally shown to be important for modulating lipid binding activity of apoE-NT. Principal component analysis of the water/propanol trajectory confirms that the region including H1' is the locus of the largest motion. Another region involves the loop connecting helix 2 and helix 3 which has been hypothesized to play the role of a hinge in the opening of the bundle.     

Umbrella Sampling Simulations of Carbon Nanoparticles Crossing Immiscible Solvents

We use molecular dynamics to compute the free energy of carbon nanoparticles crossing a hydrophobic–hydrophilic interface. The simulations are performed on a biphasic system consisting of immiscible solvents (i.e., cyclohexane and water). We solvate a carbon nanoparticle into the cyclohexane layer and use a pull force to drive the nanoparticle into water, passing over the interface. Next, we accumulate a series of umbrella sampling simulations along the path of the nanoparticle and compute the solvation free energy with respect to the two solvents. We apply the method on three carbon nanoparticles (i.e., a carbon nanocone, a nanotube, and a graphene nanosheet). In addition, we record the water-accessible surface area of the nanoparticles during the umbrella simulations. Although we detect complete wetting of the external surface of the nanoparticles, the internal surface of the nanotube becomes partially wet, whereas that of the nanocone remains dry. This is due to the nanoconfinement of the particular nanoparticles, which shields the hydrophobic interactions encountered inside the pores. We show that cyclohexane molecules remain attached on the concave surface of the nanotube or the nanocone without being disturbed by the water molecules entering the cavity.     

Effects of size constraint on water filling process in nanotube

Molecular dynamics (MD) simulation and the potential of mean force (PMF) analysis are used to investigate the structural properties of water molecules near the end of nanotube for the whole process from the initial water filling up to the configuration stabilization inside the carbon nanotubes (CNTs). Numerical simulations showed that when a small-sized nanotube is immersed into the water bath, the size constraint will induce a prevailing orientation for the water molecule to diffuse into the tube and this effect can persist approximately 3.3 angstroms from the end of CNT. As the structure within the CNTs stabilizes, the ambient structural properties can indirectly reflect their corresponding properties inside the nanotube. Our results also showed that there exists a close correlation between the PMF analysis and the results of MD simulations, and the properties at nanometer scale are closely related to the size-constraint effect.     

On the helix-coil transition in alanine based polypeptides in gas phase

Using multicanonical simulations, the authors study the effect of charged end groups on helix formation in alanine based polypeptides. They confirm earlier reports that neutral polyalanine exhibits a pronounced helix-coil transition in gas phase simulations. Introducing a charged Lys+ at the C terminal stabilizes the alpha helix and leads to a higher transition temperature. On the other hand, adding the Lys+ at the N terminal inhibits helix formation. Instead, a more globular structure was found. These results are in agreement with recent experiments on alanine based polypeptides in gas phase. They indicate that present force fields describe accurately the intramolecular interactions in proteins.     

Peptides in membranes: assessment of environmental effects via simulations using an implicit solvation model

A recently developed implicit solvation model is applied to Monte Carlo simulations of peptides in bilayer-mimetic and polar environments. The model employs the formalism of atomic solvation parameters and reproduces experimental data. Solvent effects on the␣structure of the following peptides were studied: 20-residue poly-Leu and poly-Val, transmembrane helix A of bacteriorhodopsin, magainin2. It was shown that a␣membrane-like environment considerably promotes α-helix formation (all the peptides were found to be α-helical), while simulations in water reveal helix distortion. Consistency of the results with experimental data and further implications of the model are discussed. Received: 24 April 1998 / Accepted: 3 September 1998 / Published online: 10 December 1998     

Entropy of single-file water in (6,6) carbon nanotubes

We used molecular dynamics simulations to investigate the thermodynamics of filling of a (6,6) open carbon nanotube (diameter D = 0.806 nm) solvated in TIP3P water over a temperature range from 280 K to 320 K at atmospheric pressure. In simulations of tubes with slightly weakened carbon-water attractive interactions, we observed multiple filling and emptying events. From the water occupancy statistics, we directly obtained the free energy of filling, and from its temperature dependence the entropy of filling. We found a negative entropy of about -1.3 k(B) per molecule for filling the nanotube with a hydrogen-bonded single-file chain of water molecules. The entropy of filling is nearly independent of the strength of the attractive carbon-water interactions over the range studied. In contrast, the energy of transfer depends strongly on the carbon-water attraction strength. These results are in good agreement with entropies of about -0.5 k(B) per water molecule obtained from grand-canonical Monte Carlo calculations of water in quasi-infinite tubes in vacuum under periodic boundary conditions. Overall, for realistic carbon-water interactions we expect that at ambient conditions filling of a (6,6) carbon nanotube open to a water reservoir is driven by a favorable decrease in energy, and opposed by a small loss of water entropy.     

Molecular dynamics simulations of helix-forming, amine-functionalized m-poly(phenyleneethynylene)s

We present here the results of all-atom and united-atom molecular dynamics (MD) simulations that were used to examine the folding behavior of an amine-functionalized m-poly(phenyleneethynylene) (m-PPE) oligomer in aqueous environment. The parallelized GROMACS MD simulation code and OPLS force field were used for multiple MD simulations of m-PPE oligomers containing 24 phenyl rings in extended, coiled and helix conformations separately in water to determine the minimum energy conformation of the oligomer in aqueous solvent and what interactions are most important in determining this structure. Simulation results showed that the helix is the preferred minimum energy conformation of a single oligomer in water and that Lennard-Jones interactions are the dominant forces for the stabilization of the helix. In addition, these solvophobic interactions are strong enough to maintain the helix conformation at temperatures up to 523 K.     

Theoretical Prediction of Adsorption Properties of Carmustine Drug on Various Sites of the Outer Surface of the Single-Walled Boron Nitride Nanotube and Investigation of Urea Effect on Drug Delivery by DFT and MD

In this work, the adsorption behavior of Carmustine (BCNU) drug over the (6,0) zigzag single-wall boron nitride nanotube (SWBNNT) is studied by means of density functional theory calculations and molecular dynamics simulations (MD). The calculated adsorption energies proved that the adsorption of BCNU molecule on SWBNNT is a physisorption process. The natural bond orbital calculations demonstrated that existence of a charge transfer from the SWBNNT to the BCNU molecule. Moreover, quantum theory of atoms in molecules showed that the hydrogen bonds and electrostatic interactions are two major factors contributed to the overall stabilities of the complexes. Furthermore, interaction of BCNU with the surface of single wall BNNT at 310 K and 1 bar in the present of water and different concentration of Urea molecules has been studied by MD simulation. The MD results confirm that the highest number of hydrogen bond and the lowest value of Lennard-Jones (L-J) energy between nanotube and drug exist in the simulation system with concentration of 1 mol L^?1 Urea.     

DFT Study of Physisorption Effect of the Curcumin on CNT(8,0-6) Nanotube for Biological Applications

In the given work the adsorption properties of molecule curcumin((1 E,6 E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) on CNT(8,0-6) nanotube were investigated by the density functional theory(DFT) in the solvent water for the first time. The non-bonded interaction effects of compounds curcumin and CNT(8,0-6) nanotube on the electronic properties, UV/Vis spectra, chemical shift tensors and natural charges were determined and discussed. The electronic spectra of the compound curcumin and the complex CNT(8,0-6)/curcumin in the solvent water were calculated by time dependent density functional theory(TD-DFT) for investigation of the maximum wavelength value of molecule Curcumin before and after the non-bonded interaction with the CNT(8,0-6) nanotube and molecular orbitals involved in the formation of absorption spectrum of the complex CNT(8,0-6)/curcumin at maximum wavelength.     

尿素/氧化三甲胺混合溶剂影响单壁碳纳米管内部水合性质的分子动力学模拟

尿素是早已被人们认识的蛋白质变性剂,而氧化三甲胺则是最常用的蛋白质结构保护剂。虽然多年来被广泛应用在生物实验中,但是它们是如何在蛋白质结构形成中起作用,特别是氧化三甲胺是如何在高浓度尿素环境中起到抑制尿素蛋白变性作用的分子机制,至今仍然没有得到圆满解答。本文以单壁碳纳米管为模型疏水体系,采用分子动力学模拟研究尿素/氧化三甲胺混合溶液中纳米管内部水合性质,结果表明氧化三甲胺更易与水分子和尿素分子形成较强相互作用从而稳定了水溶液结构,这一结果亦表明了氧化三甲胺可以通过间接机制抵消尿素分子对于碳纳米管内部水合性质的影响。     

Effects of charge distribution on water filling process in carbon nanotube

Using umbrella sampling technique with molecular dynamics simulation, we investigated the nanofluidic transport of water in carbon nanotube (CNT). The simulations showed that a positive charge modification to the carbon nanotube can slow down the water column growth process, while the negative charge modification to the carbon nanotube will, on the other hand, quicken the water column growth process. The free energy curves were obtained through the statistical process of water column growth under different charge distributions, and the results indicated that these free energy curves can be employed to explain the dynamical process of water column growth in the nanosized channels. Supported by the National Natural Science Foundation of China (Grant Nos. 10425420 and 20773145), the Ministry of Science and Technology of China (Grant Nos. 2006CB806200 and 2006CB932100), and the Chinese Academy of Sciences including its CNIC Supercomputer Center.     

Interaction of water with DNA single and double helix in the B conformation

The interaction energy between water and B-DNA in the single and double helix is computed at a number of planar cross sections perpendicular to the helix long axis and for a few cylindrical surfaces enclosing the helix. In addition, Monte Carlo simulations are presented for a small cluster of water around regions of energy minima. On the base of these simulations the structure of water for B-DNA in solution, the quaternary structure of B-DNA, is proposed and discussed. The intermolecular interaction used in the Monte Carlo computation has been derived from ab initio computations of complexes between water and the DNA bases, diethylphosphate, a ribose derivative, and other model compounds.     

Thermodynamics of water entry in hydrophobic channels of carbon nanotubes

Experiments and computer simulations demonstrate that water spontaneously fills the hydrophobic cavity of a carbon nanotube. To gain a quantitative thermodynamic understanding of this phenomenon, we use the recently developed two phase thermodynamics method to compute translational and rotational entropies of confined water molecules inside single-walled carbon nanotubes and show that the increase in energy of a water molecule inside the nanotube is compensated by the gain in its rotational entropy. The confined water is in equilibrium with the bulk water and the Helmholtz free energy per water molecule of confined water is the same as that in the bulk within the accuracy of the simulation results. A comparison of translational and rotational spectra of water molecules confined in carbon nanotubes with that of bulk water shows significant shifts in the positions of the spectral peaks that are directly related to the tube radius.     

Solvent effect on the folding dynamics and structure of E6-associated protein characterized from ab initio protein folding simulations

Solvent effect on protein conformation and folding mechanism of E6-associated protein (E6ap) peptide are investigated using a recently developed charge update scheme termed as adaptive hydrogen bond-specific charge (AHBC). On the basis of the close agreement between the calculated helix contents from AHBC simulations and experimental results, we observed based on the presented simulations that the two ends of the peptide may simultaneously take part in the formation of the helical structure at the early stage of folding and finally merge to form a helix with lowest backbone RMSD of about 0.9 A? in 40% 2,2,2-trifluoroethanol solution. However, in pure water, the folding may start at the center of the peptide sequence instead of at the two opposite ends. The analysis of the free energy landscape indicates that the solvent may determine the folding clusters of E6ap, which subsequently leads to the different final folded structure. The current study demonstrates new insight to the role of solvent in the determination of protein structure and folding dynamics.     

The role of activation energy and reduced viscosity on the enhancement of water flow through carbon nanotubes

Molecular dynamics simulations are carried out to study the pressure driven fluid flow of water through single walled carbon nanotubes. A method for the calculation of viscosity of the confined fluid based on the Eyring theory of reaction rates is proposed. The method involves the calculation of the activation energy directly from the molecular dynamics trajectory information. Computations are performed using this method to study the effect of surface curvature on the confined fluid viscosity. The results indicate that the viscosity varies nonlinearly with the carbon nanotube diameter. It is concluded that the reason behind the observed enhancement in the rate of fluid flow through carbon nanotubes could be the nonlinear variation of viscosity.     

A generalized Born formalism for heterogeneous dielectric environments: application to the implicit modeling of biological membranes

Reliable computer simulations of complex biological environments such as integral membrane proteins with explicit water and lipid molecules remain a challenging task. We propose a modification of the standard generalized Born theory of homogeneous solvent for modeling the heterogeneous dielectric environments such as lipid/water interfaces. Our model allows the representation of biological membranes in the form of multiple layered dielectric regions with dielectric constants that are different from the solute cavity. The proposed new formalism is shown to predict the electrostatic component of solvation free energy with a relative error of 0.17% compared to exact finite-difference solutions of the Poisson equation for a transmembrane helix test system. Molecular dynamics simulations of melittin and bacteriorhodopsin are carried out and performed over 10 ns and 7 ns of simulation time, respectively. The center of melittin along the membrane normal in these stable simulations is in excellent agreement with the relevant experimental data. Simulations of bacteriorhodopsin started from the experimental structure remained stable and in close agreement with experiment. We also examined the free energy profiles of water and amino acid side chain analogs upon membrane insertion. The results with our implicit membrane model agree well with the experimental transfer free energy data from cyclohexane to water as well as explicit solvent simulations of water and selected side chain analogs.