Folding and translocation of the undecamer of poly-L-leucine across the water-hexane interface. A molecular dynamics study.

The undecamer of poly-L-leucine at the water-hexane interface is studied by molecular dynamics simulations. This represents a simple model relevant to folding and insertion of hydrophobic peptides into membranes. The peptide, initially placed in a random coil conformation on the aqueous side of the system, rapidly translocates toward the hexane phase and undergoes interfacial folding into an alpha-helix in the subsequent 36 ns. Folding is nonsequential and highly dynamic. The initially formed helical segment at the N-terminus of the undecamer becomes transiently broken and, subsequently, reforms before the remainder of the peptide folds from the C-terminus. The formation of intramolecular hydrogen bonds during the folding of the peptide is preceded by a dehydration of the participating polar groups, as they become immersed in hexane. Folding proceeds through a short-lived intermediate, a 3(10)-helix, which rapidly interconverts to an alpha-helix. Both helices contribute to the equilibrium ensemble of folded structures. The helical peptide is largely buried in hexane, yet remains adsorbed at the interface. Its preferred orientation is parallel to the interface, although the perpendicular arrangement with the N-terminus immersed in hexane is only slightly less favorable. In contrast, the reversed orientation is highly unfavorable, because it would require dehydration of C-terminus carbonyl groups that do not participate in intramolecular hydrogen bonding. For the same reason, the transfer of the undecamer from the interface to the bulk hexane is also unfavorable. The results suggest that hydrophobic peptides fold in the interfacial region and, simultaneously, translocate into the nonpolar side of the interface. It is further implied that peptide insertion into the membrane is accomplished by rotating from the parallel to the perpendicular orientation, most likely in such a way that the N-terminus penetrates the bilayer.     

Structure and Energetics of model amphiphilic molecules at the water liquid-vapor interface. A molecular dynamics study

A molecular dynamics study of adsorption of p-n-pentylphenol at infinite dilution at the water liquid-vapor interface is reported. The calculated free energy of adsorption is -8.8 +/- 0.7 kcal/mol, in good agreement with the experimental value of -7.3 kcal/mol. The transition between the interfacial region and the bulk solution is sharp and well-defined by energetic, conformational, and orientational criteria. At the water surface, the phenol head group is mostly immersed in aqueous solvent. The most frequent orientation of the hydrocarbon tail is parallel to the interface, due to dispersion interactions with the water surface. This arrangement of the phenol ring and the alkyl chain requires that the chain exhibits a kink. As the polar head group is being moved into the solvent, the chain length increases and the tail becomes increasingly aligned toward the surface normal, such that the nonpolar part of the molecule exposed to water is minimized. The same effect was achieved when phenol was replaced by a more polar head group, phenolate. This result underscores the difference between hydrophobic hydration at the surface and in the bulk solvent, when nonpolar molecular fragments adopt compact conformations.     

A molecular dynamics study of the pentacyclo-undecane cage amino acid tripeptide

In this paper, we report on the conformational profile of the pentacyclo-undecane (PCU) cage tripeptide carried out by molecular dynamics (MD) simulation using water as an explicit solvent. The MD solution phase studies carried on the model peptide analogues (A)=Ac–Ala–Ala–Ala–NHMe; (B)=Ac–Cage–Cage–Cage–NHMe; (C)=Ac–Ala–Cage–Ala–NHMe and (D)=Ac–Ala–Pro–Ala–NHMe, are used as a complimentary technique to the corresponding gas phase simulated annealing (SA) study previously carried out in our laboratory. No significant structural changes were observed over the MD trajectories. However, the results reported here provide further evidence that the (PCU) cage amino acid exhibits C_7eq, C_7aq, _R and _L conformations, and the theoretical results suggest that the PCU cage amino acid is a strong β-turn inducer. These results support the prediction that when the PCU cage residues are in the (i) and (i+2) positions, the β-turn can be extended in either direction to form anti-parallel β-pleated sheets, thereby forming the basis of the mechanism for the folding back of the chain in a cross-β-turn structure.     

Adsorption of alpha amino acids at the water/goethite interface

The adsorption of amino acids onto mineral surfaces plays an important role in a wide range of areas, e.g., low-temperature aqueous geochemistry, bone formation and protein-bone interactions. In this work, the adsorption of three alpha aminoacids (sarcosine, MIDA and EDDA) onto goethite (alpha-FeOOH) was studied as a function of pH and background electrolyte concentration at 25.0 degrees C, and the molecular structures of the surface complexes formed were analyzed by means of ATR-FTIR spectroscopy. The results showed that adsorption of alpha amino acids were strongly dependent on the functionality and structure of the ligands. No adsorption was detected for the zwitterionic sarcosine indicating that simple alpha amino acids without other ionizable and/or functional groups display insignificant affinity for mineral surfaces such as goethite. With respect to the more complex amino acids, which are surface reactive, the number and relative positions of carboxylate and amine groups determine the types of surface interactions. These interactions range from non-specific outer-sphere to specific inner-sphere interactions as shown by the MIDA and EDDA results, respectively. The results presented herein suggest that isomerically-selective adsorption might only occur for amino acids that are capable of specific surface interactions, either through site-specific hydrogen bonding or inner-sphere complexation.     

Phase behavior of amphiphiles at liquid crystals/water interface: A coarse-grained molecular dynamics study

We present a coarse-grained molecular dynamics simulation study of phase behavior of amphiphilic monolayers at the liquid crystal （LC）/water interface. The results revealed that LCs at interface can influence the lateral ordering of amphiphiles. Particularly, the amphiphile tails along with perpendicularly penetrated LCs between tails undergo a two-dimension phase transition from liquid-expanded into a liquid-condensed phase as their area density at interface reaches 0.93. While, the liquid-condensed phase of the monolayer never appears at oil/water interface with isotropic shape oil particles. These findings reveal the penetration of anisotropic LC can promote ordered lateral organization of amphiphiles. Moreover, we find the phase transition point is shifted to lower surface coverage of amphiphiles when the LCs have larger affinity to the amphiphile tails.     

Adsorption and solvation of ethanol at the water liquid-vapor interface: a molecular dynamics study

The free energy profiles of methanol and ethanol at the water liquid-vapor interface at 310K were calculated using molecular dynamics computer simulations. Both alcohols exhibit a pronounced free energy minimum at the interface and, therefore, have positive adsorption at this interface. The surface excess was computed from the Gibbs adsorption isotherm and was found to be in good agreement with experimental results. Neither compound exhibits a free energy barrier between the bulk and the surface adsorbed state. Scattering calculations of ethanol molecules from a gas phase thermal distribution indicate that the mass accommodation coefficient is 0.98, and the molecules become thermalized within 10 ps of striking the interface. It was determined that the formation of the solvation structure around the ethanol molecule at the interface is not the rate-determining step in its uptake into water droplets. The motion of an ethanol molecule in a water lamella was followed for 30 ns. The time evolution of the probability distribution of finding an ethanol molecule that was initially located at the interface is very well described by the diffusion equation on the free energy surface.     

Isomerization reaction dynamics and equilibrium at the liquid-vapor interface of water. A molecular-dynamics study

The gauche-trans isomerization reaction of 1,2-dichloroethane at the liquid-vapor interface of water is studied using molecular-dynamics computer simulations. The solvent bulk and surface effects on the torsional potential of mean force and on barrier recrossing dynamics are computed. The isomerization reaction involves a large change in the electric dipole moment, and as a result the trans/gauche ratio is considerably affected by the transition from the bulk solvent to the surface. Reactive flux correlation function calculations of the reaction rate reveal that deviation from the transition-state theory due to barrier recrossing is greater at the surface than in the bulk water. This suggests that the system exhibits non-Rice-Ramsperger-Kassel-Marcus behavior due to the weak solvent-solute coupling at the water liquid-vapor interface.     

Gemini surfactants at the air/water interface: a fully atomistic molecular dynamics study

Gemini surfactants typically consist of two single-chain surfactants chemically linked by a spacer molecule. We report herein the results of fully atomistic molecular dynamics (MD) simulations of a series of Gemini surfactants: CsH2s-alpha,omega-bis(C12H25N+(CH3)2Cl-), at the air/water interface with s = 3, 4, 6, 12, 14, and 16, at values of the initial surface area per surfactant AS = 70 A2, 77 A2, 95 A2, 151 A2, 133 A2, and 103 A2, respectively. The AS values employed were obtained from surface tension and neutron reflection experiments at the respective cmc of each surfactant. The Gemini surfactant corresponding to s = 3 was also simulated at AS = 105 A2, which is the experimentally derived value of surface area per surfactant at 1/10th of cmc. Only the surfactants with s = 12 and 14 and the surfactant with s = 3 at AS = 105 A2 gave a stable monolayer at the air/water interface. In other cases, we observe movement of some surfactant molecules from the air/water interface into the aqueous phase, resulting in a stable primary monolayer of surfactants at the air/water interface and a small concentration of surfactant molecules below it. The latter form aggregates, with their hydrophobic chains in the core. The density profiles along the normal to the interface are compared with the ones obtained from neutron reflection experiments. The MD simulations confirm the bending of the spacer toward the hydrophobic chains as the spacer length is increased and the spacer becomes more hydrophobic. The simulations have helped to shed light on the low-resolution picture which emerges from experimental analyses.     

A molecular dynamics study of the complexation of tryptophan,phenylalanine and tyrosine amino acids with cucurbit[7]uril

Journal of Inclusion Phenomena and Macrocyclic Chemistry - Molecular dynamics simulations were performed in aqueous solution to elucidate an atomistic level picture of complex formation between...     

Conformational study of insect adipokinetic hormones using NMR constrained molecular dynamics

Mem-CC (pGlu-Leu-Asn-Tyr-Ser-Pro-Asp-Trp-NH₂), Tem-HrTH (pGlu-Leu-Asn-Phe-Ser-Pro-Asn-Trp-NH₂) and Del-CC (pGlu-Leu-Asn-Phe-Ser-Pro-Asn-Trp-Gly-Asn-NH₂) are adipokinetic hormones, isolated from the corpora cardiaca of different insect species. These hormones regulate energy metabolism during flight and so are intimately involved in an insect's mobility. Secondary structural elements of these peptides and the N7 analogue, [N7]-Mem-CC (pGlu-Leu-Asn-Tyr-Ser-Pro-Asn-Trp-NH₂), have been determined in dimethylsulfoxide solution using NMR restrained molecular mechanic simulations. The neuropeptides were all found to have an extended structure for the first 4 residues and a -turn between residues 4–8. For Tem-HrTH and Del-CC, asparagine (N7) which is postulated to be involved in receptor binding and/or activation, projects outward form the -turn. Mem-CC does not have an asparagine at position 7 while, for [N7]-Mem-CC, the N7 sidechain folds inside the -turn preventing its interaction with the receptor.     

Conformational dynamics of the nicotinic acetylcholine receptor channel: a 35-ns molecular dynamics simulation study

The nicotinic acetylcholine receptor (AChR) is the paradigm of ligand-gated ion channels, integral membrane proteins that mediate fast intercellular communication in response to neurotransmitters. A 35-ns molecular dynamics simulation has been performed to explore the conformational dynamics of the entire membrane-spanning region, including the ion channel pore of the AChR. In the simulation, the 20 transmembrane (TM) segments that comprise the whole TM domain of the receptor were inserted into a large dipalmitoylphosphatidylcholine (DPPC) bilayer. The dynamic behavior of individual TM segments and their corresponding AChR subunit helix bundles was examined in order to assess the contribution of each to the conformational transitions of the whole channel. Asymmetrical and asynchronous motions of the M1-M3 TM segments of each subunit were revealed. In addition, the outermost ring of five M4 TM helices was found to convey the effects exerted by the lipid molecules to the central channel domain. Remarkably, a closed-to-open conformational shift was found to occur in one of the channel ring positions in the time scale of the present simulations, the possible physiological significance of which is discussed.     

Reflection anisotropy spectroscopy study of the adsorption of sulfur-containing amino acids at the Au(110)/electrolyte interface

Protein interactions with surfaces are key to understanding the behavior of implantable medical devices. The optical technique of reflection anisotropy spectroscopy (RAS) has considerable potential for the study of interactions between important biological molecules and surfaces. This study used RAS to investigate the adsorption of S amino acids onto Au(110) in a liquid environment under different conditions of potential and pH. Certain spectral features can be associated with the Au(110), as reported previously, while other features are assigned to bonds between the amino acids and the Au surface. The RA spectra are shown to be influenced by the structure of the amino acid, the solution pH, and the applied electrode potential. This work has assigned the negative feature at 2.5 eV to the Au-thiolate, bond while the positive feature at 2.5 eV is assigned to the disulfide bond. The broad spectral feature at 3.5 eV is attributed to the Au-amino interaction, while the sharper feature at slightly higher energy is associated with the Au-carboxylate interaction. Sulfur-containing amino acids are frequently found on the outside of protein molecules and could be used to anchor the protein to the surface.     

Liquid-vapor interface of methanol-water mixtures: a molecular dynamics study

Molecular dynamics simulations were carried out to investigate the structural and thermodynamic properties and variations in the dipole moments of the liquid-vapor interfaces of methanol-water mixtures. Various methanol-water compositions were simulated at room temperature. We found that methanol tends to concentrate at the interface, and the computed surface tension shows a composition dependence that is consistent with experimental measurements. The methanol molecule shows preferred orientation near the interface with the methyl group pointing into the vapor phase. The methanol in the mixture is found to have larger dipole moments than that of pure liquid methanol. The strong local field induced by the surrounding water molecules is partly the reason for this difference. The dependence of hydrogen-bonding patterns between methanol and water on the interface and the composition of the mixture is also discussed in the paper.     

Synergistic effect of dicarbollide anions in liquid-liquid extraction: a molecular dynamics study at the octanol-water interface

We report a molecular dynamics study of chlorinated cobalt bis(dicarbollide) anions [(B(9)C(2)H(8)Cl(3))(2)Co](-)"CCD(-)" in octanol and at the octanol-water interface, with the main aim to understand why these hydrophobic species act as strong synergists in assisted liquid-liquid cation extraction. Neat octanol is quite heterogeneous and is found to display dual solvation properties, allowing to well solubilize CCD(-), Cs(+) salts in the form of diluted pairs or oligomers, without displaying aggregation. At the aqueous interface, octanol behaves as an amphiphile, forming either monolayers or bilayers, depending on the initial state and confinement conditions. In biphasic octanol-water systems, CCD(-) anions are found to mainly partition to the organic phase, thus attracting Cs(+) or even more hydrophilic counterions like Eu(3+) into that phase. The remaining CCD(-) anions adsorb at the interface, but are less surface active than at the chloroform interface. Finally, we compare the interfacial behavior of the Eu(BTP)(3)(3+) complex in the absence and in the presence of CCD(-) anions and extractant molecules. It is found that when the CCD(-)'s are concentrated enough, the complex is extracted to the octanol phase. Otherwise, it is trapped at the interface, attracted by water. These results are compared to those obtained with chloroform as organic phase and discussed in the context of synergistic effect of CCD(-) in liquid-liquid extraction, pointing to the importance of dual solvation properties of octanol and of the hydrophobic character of CCD(-) for synergistic extraction of cations.     

Proton transfer at the carboxylic sites of amino acids: A single water molecule catalyzed process

Ab initio calculations at MP2 level of theory were used to study the proton transfer at the carboxylic sites of amino acids, in the isolated, mono‐ and di‐hydrated forms. In the case of water dimer, two interaction modes with glycine neutral structures (see Fig. 3 ) were explored, corresponding to the concerted and stepwise reaction pathways. Their transition states can be described as (H₂O? H? OH₂)⁺ [Fig. 4 (a)] and (H₂O‐‐‐H? OH₂)⁺ [Fig. 4 (b)], respectively. The energy analysis indicated that the concerted pathway is preferred. In the isolated, mono‐ and di‐hydrated glycine complexes, the activation barriers of the proton transfer at the carboxylic sites were calculated to be 34.49, 16.59, and 13.36 kcal mol^?1, respectively. It was thus shown that the proton transfer is significantly assisted and catalyzed by water monomer so that it can take place at room temperature. Instead, the further addition of water molecules plays solvent effects rather than catalytic effects to this proton transfer process. The above results obtained with discrete water molecules were supported by the solvent continuum calculated data. It was also observed that the heavy dependence of the solvent continuum models on dipole moments may produce misleading results. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009     

Molecular theory on dielectric constant at interfaces: a molecular dynamics study of the water/vapor interface

Though the local dielectric constant at interfaces is an important phenomenological parameter in the analysis of surface spectroscopy, its microscopic definition has been uncertain. Here, we present a full molecular theory on the local field at interfaces with the help of molecular dynamics simulation, and thereby provide microscopic basis for the local dielectric constant so as to be consistent to the phenomenological three-layer model of interface systems. To demonstrate its performance, we applied the theory to the water/vapor interface, and obtained the local field properties near the interface where the simple dielectric model breaks down. Some computational issues pertinent to Ewald calculations of the dielectric properties are also discussed.     

Separation of amino acids in glucose isomerase crystal: Insight from molecular dynamics simulations

The separation of amino acids (Arg, Phe and Trp) in a liquid chromatography is investigated using molecular dynamics simulations. A bioorganic nanoporous material – glucose isomerase crystal – is used as the stationary phase and water as the mobile phase. The transport velocities of amino acids decrease in the order Arg > Phe > Trp, consistent with experimental measurement. The elution order is not affected by the solute concentration or by the flowing rate of mobile phase. Arg is highly hydrophilic and charged, interacts with water the most strongly, and thus moves with flowing water the fastest. Trp has the largest van der Waals volume and encounters the largest steric hindrance, leading to the slowest velocity. From the number distributions of amino acids around protein surface, Trp and Phe are found to stay closer to protein than Arg. The solvent-accessible surface areas of amino acids and the numbers of hydrogen bonds between amino acids and water further elucidate the observed velocity difference. The simulation results provide useful microscopic insight into the retention mechanisms in chromatographic separation process and suggest that glucose isomerase crystal has the capability to separate amino acids.     

Studies on synthesis and molecular dynamics simulation of dendrimers containing amino acids and peptides

A series of poly(ether-amide) dendrimers with amino acids and peptides as the peripheral functional groups was synthesized, and their structures were confirmed by nuclear magnetic resonance (NMR) and electrospray ionization-mass spectrometry (ESI-MS) spectrometry. Molecular dynamics simulation of the peptide dendrimers in solution was performed, indicating that, the prior conformations of the dendrimers were atom number dependent, i.e., with the increases of the atom number, the prior conformations were more spherical. Also, the amino acid α-C atom radial distribution indicated that, with larger peripheral groups, more back-folding of the dendrimers occurred. __________ Translated from Acta Chimica Sinica, 2007, 65(1): 21–26 [译自: 化学 通报]     

Incorporation dynamics of molecular guests into two-dimensional supramolecular host networks at the liquid-solid interface

The objective of this work is to study both the dynamics and mechanisms of guest incorporation into the pores of 2D supramolecular host networks at the liquid-solid interface. This was accomplished by adding molecular guests to prefabricated self-assembled porous monolayers and the simultaneous acquisition of scanning tunneling microscopy (STM) topographs. The incorporation of the same guest molecule (coronene) into two different host networks was compared, where the pores of the networks either featured a perfect geometric match with the guest (for trimesic acid host networks) or were substantially larger than the guest species (for benzenetribenzoic acid host networks). Even the moderate temporal resolution of standard STM experiments in combination with a novel injection system was sufficient to reveal clear differences in the incorporation dynamics in the two different host networks. Further experiments were aimed at identifying a possible solvent influence. The interpretation of the results is aided by molecular mechanics (MM) and molecular dynamics (MD) simulations.