Long-range Electrostatic Forces Research Articles

The Effect of Membrane Composition and Protein Lipidation on the Affinity and Structure of the HIV-1 MA Domain

The retroviral polyprotein Gag is the single essential component required for the formation of new HIV-1 viral particles. Gag proteins are initially expressed in the cellular cytoplasm but eventually target the surface of the plasma membrane (PM) where the assembly occurs. The N-terminal matrix (MA) domain of Gag is the key structural motif that mediates targeting. Several biochemical mechanisms are implicated in MA-membrane binding including electrostatic interactions between a patch of basic residues and anionic lipids, a hydrophobic interaction with a myristolated amino acid group and specific binding to phophatidylinositol 4,5-bisphosphate PI(4,5)P2 found only in the PM. In fact PI(4,5)P2 binding may be a mechanism for directing Gag assembly to specific regions of the PM and potentially induces myristate exposure from a sequestered state within the protein.To establish the molecular interactions that controls MA-membrane coupling, we conducted surface plasmon resonance(SPR) experiments to determine binding affinities on different membranes composition using both myristolated and non-myristolated MA. Charge density of the lipid membrane had a clear effect on membrane association resulting in high surface coverage. Myristolation significantly increased affinity by more than an order of magnitude. The coupling between binding and orientation of the HIV-1 MA domain on the membrane is investigated by neutron reflectivity. The additional anchoring mechanisms may alter the membrane-binding interface of MA or fix the orientation further. Lipid targeting by the MA domain is a crucial step in viral assembly and may be directed by a hierarchy of biochemical interactions beginning with long-range but weak electrostatic forces and followed by a localized PI(4,5)P2/myristate exposure mechanism for further anchoring. These molecular details may provide a general understanding of how peripheral membrane proteins make reversible and specific interactions with the membrane.

Effect of the Reaction Field on Molecular Forces and Torques Revealed by an Image-Charge Solvation Model.

We recently developed the Image-Charge Solvation Model (ICSM), which is an explicit/implicit hybrid model to accurately account for long-range electrostatic forces in molecular dynamics simulations [Lin et al., J. Chem. Phys., 131, 154103, 2009]. The ICSM has a productive spherical volume within the simulation cell for which key physical properties of bulk water are reproduced, such as density, radial distribution function, diffusion constants and dielectric properties. Although the reaction field (RF) is essential, it typically accounts for less than 2% of the total electrostatic force on a water molecule. This observation motivates investigating further the role of the RF within the ICSM. In this report we focus on distributions of forces and torques on water molecules as a function of distance from the origin and make extensive tests over a range of model parameters where Coulomb forces are decomposed into direct interactions from waters modeled explicitly and the RF. Molecular torques due to the RF typically account for 20% of the total torque, revealing why the RF plays an important role in the dielectric properties of simulated water. Moreover, it becomes clear that the buffer layer in the ICSM is essential to mitigate artifacts caused by the discontinuous change in dielectric constants at the explicit/implicit interface.

Dual Effect of Phosphatidyl (4,5)-Bisphosphate PIP2 on Shaker K+ Channels

Dual Effect of Phosphatidyl (4,5)-Bisphosphate PIP2 on Shaker K+ Channels

Electromagnetic fluctuation-induced interactions in randomly charged slabs

Randomly charged net-neutral dielectric slabs are shown to interact across a featureless dielectric continuum with long-range electrostatic forces that scale with the statistical variance of their quenched random charge distribution and inversely with the distance between their bounding surfaces. By accounting for the whole spectrum of electromagnetic field fluctuations, we show that this long-range disorder-generated interaction extends well into the retarded regime where higher order (non-zero) Matsubara frequencies contribute significantly. This occurs even for highly clean samples with only a trace amount of charge disorder and shows that disorder effects can be important down to the nanoscale. As a result, the previously predicted non-monotonic behavior for the total force between dissimilar slabs as a function of their separation distance is substantially modified by higher order contributions, and in almost all cases of interest, we find that the equilibrium inter-surface separation is shifted to substantially larger values compared to predictions based solely on the zero-frequency component. This suggests that the ensuing non-monotonic interaction is more easily amenable to experimental detection. The presence of charge disorder in the intervening dielectric medium between the two slabs is shown to lead to an additional force that can be repulsive or attractive depending on the system parameters and can, for instance, wash out the non-monotonic behavior of the total force when the intervening slab contains a sufficiently large amount of disorder charges.

Imaging soft matters in water with torsional mode atomic force microscopy

We have developed a high-sensitivity atomic force microscopy (AFM) mode operated in aqueous environment based on the torsional resonance of the cantilever. It is found that the torsional mode can achieve a good spatial resolution even with a relatively large tip. We have used this mode to image different soft materials in water, including DNA molecules and purple membrane. High-resolution images of purple membrane can be obtained at a relatively low ion concentration under a long-range electrostatic force. Thus the torsional mode allows investigators to probe surface structures and their properties under a wide range of solution conditions.

Prediction of vapor–liquid equilibrium and PVTx properties of geological fluid system with SAFT-LJ EOS including multi-polar contribution. Part II: Application to H2O–NaCl and CO2–H2O–NaCl System

The SAFT-LJ equation of state improved by Sun and Dubessy (2010) can represent the vapor–liquid equilibrium and PVTx properties of the CO2–H2O system over a wide P–T range because it accounts for the energetic contribution of the main types of molecular interactions in terms of reliable molecular based models. Assuming that NaCl fully dissociates into individual ions (spherical Na+ and Cl−) in water and adopting the restricted primitive model of mean spherical approximation to account for the energetic contribution due to long-range electrostatic forces between ions, this study extends the improved SAFT-LJ EOS to the H2O–NaCl and the CO2–H2O–NaCl systems at temperatures below 573K. The EOS parameters for the interactions between ion and ion and between ion and water were determined from the mean ionic activity coefficient data and the density data of the H2O–NaCl system. The parameters for the interactions between ion and CO2 were evaluated from CO2 solubility data of the CO2–H2O–NaCl system. Comparison with the experimental data shows that this model can predict the mean ionic activity coefficient, osmotic coefficient, saturation pressure, and density of aqueous NaCl solution and can predict the vapor–liquid equilibrium and PVTx properties of the CO2–H2O–NaCl system over the range from 273 to 573K, from 0 to 1000bar, and from 0 to 6mol/kg NaCl with high accuracy.

Peculiarities of three-passage measurements in magnetic force microscopy

The method of three-passage measurements in magnetic force microscopy is described, which yields refined magnetic images of nano and microobjects, and eliminates the possible parasitic influence of long-range electrostatic forces while obtaining a magnetic image.

Implementing molecular dynamics on hybrid high performance computers – Particle–particle particle-mesh

The use of accelerators such as graphics processing units (GPUs) has become popular in scientific computing applications due to their low cost, impressive floating-point capabilities, high memory bandwidth, and low electrical power requirements. Hybrid high-performance computers, machines with nodes containing more than one type of floating-point processor (e.g. CPU and GPU), are now becoming more prevalent due to these advantages. In this paper, we present a continuation of previous work implementing algorithms for using accelerators into the LAMMPS molecular dynamics software for distributed memory parallel hybrid machines. In our previous work, we focused on acceleration for short-range models with an approach intended to harness the processing power of both the accelerator and (multi-core) CPUs. To augment the existing implementations, we present an efficient implementation of long-range electrostatic force calculation for molecular dynamics. Specifically, we present an implementation of the particle–particle particle-mesh method based on the work by Harvey and De Fabritiis. We present benchmark results on the Keeneland InfiniBand GPU cluster. We provide a performance comparison of the same kernels compiled with both CUDA and OpenCL. We discuss limitations to parallel efficiency and future directions for improving performance on hybrid or heterogeneous computers.

Molecular basis of proton uptake in single and double mutants of cytochromec oxidase

Cytochrome c oxidase, the terminal enzyme of the respiratory chain, utilizes the reduction of dioxygeninto water to pump protons across the mitochondrial inner membrane. The principalpathway of proton uptake into the enzyme, the D channel, is a 2.5 nm long channel-likecavity named after a conserved, negatively charged aspartic acid (D) residue thought tohelp recruiting protons to its entrance (D132 in the first subunit of the S. sphaeroidesenzyme). The single-point mutation of D132 to asparagine (N), a neutral residue,abolishes enzyme activity. Conversely, replacing conserved N139, one-third into the Dchannel, by D, induces a decoupled phenotype, whereby oxygen reduction proceedsbut not proton pumping. Intriguingly, the double mutant D132N/N139D, whichconserves the charge of the D channel, restores the wild-type phenotype. We usemolecular dynamics simulations and electrostatic calculations to examine thestructural and physical basis for the coupling of proton pumping and oxygenchemistry in single and double N139D mutants. The potential of mean force for theconformational isomerization of N139 and N139D side chains reveals the presence of threerotamers, one of which faces the channel entrance. This out-facing conformer ismetastable in the wild-type and in the N139D single mutant, but predominant in thedouble mutant thanks to the loss of electrostatic repulsion with the carboxylategroup of D132. The effects of mutations and conformational isomerization on thepKa of E286, an essential proton-shuttling residue located at the top of the D channel, areshown to be consistent with the electrostatic control of proton pumping proposed recently(Fadda et al 2008 Biochim. Biophys. Acta 1777 277–84). Taken together, these resultssuggest that preserving the spatial distribution of charges at the entrance of the D channelis necessary to guarantee both the uptake and the relay of protons to the active site of theenzyme. These findings highlight the interplay of long-range electrostatic forces and localstructural fluctuations in the control of proton movement and provide a physicalexplanation for the restoration of proton pumping activity in the double mutant.

Investigating the cationic side chains of the antimicrobial peptide tritrpticin: Hydrogen bonding properties govern its membrane-disruptive activities

The positively charged side chains of cationic antimicrobial peptides are generally thought to provide the initial long-range electrostatic attractive forces that guide them towards the negatively charged bacterial membranes. Peptide analogs were designed to examine the role of the four Arg side chains in the cathelicidin peptide tritrpticin (VRRFPWWWPFLRR). The analogs include several noncoded Arg and Lys derivatives that offer small variations in side chain length and methylation state. The peptides were tested for bactericidal and hemolytic activities, and their membrane insertion and permeabilization properties were characterized by leakage assays and fluorescence spectroscopy. A net charge of +5 for most of the analogs maintains their high antimicrobial activity and directs them towards preferential insertion into model bacterial membrane systems with a similar extent of burial of the Trp side chains. However the peptides exhibit significant functional differences. Analogs with methylated cationic side chains cause lower levels of membrane leakage and are associated with lower hemolytic activities, making them potentially attractive pharmaceutical candidates. Analogs containing the Arg guanidinium groups cause more membrane disruption than those containing the Lys amino groups. Peptides in the latter group with shorter side chains have increased membrane activity and conversely, elongating the Arg residue causes slightly higher membrane activity. Altogether, the potential for strong hydrogen bonding between the four positive Arg side chains with the phospholipid head groups seems to be a determinant for the membrane disruptive properties of tritrpticin and many related cationic antimicrobial peptides.

Electrochemical and surface analysis studies on corrosion inhibition of Q235 steel by imidazoline derivative against CO 2 corrosion

The inhibition performance of a newly synthesized thioureido imidazoline inhibitor (TAI) in CO 2 corrosion was studied by using electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). Results show that the values of inhibition efficiency show peak-value-phenomenon at concentration of 0.15 mmol dm −3 owing to the change of adsorption mode. The adsorption of protonated TAI molecules on the negatively charged steel surface makes the potential of zero charge (PZC) shift to positive direction, and the long-range electrostatic exclusive forces between AFM tip and sample surface are reduced by screening effect of surface charges.

Reversed Anionic Hofmeister Series: The Interplay of Surface Charge and Surface Polarity

We describe a two-scale modeling approach toward anion specificity at surfaces of varying charge and polarity. Explicit-solvent atomistic molecular dynamics simulations at neutral hydrophobic (i.e., nonpolar) and neutral hydrophilic (i.e., polar) self-assembled monolayers furnish potentials of mean force for Na(+) and the halide anions F(-), Cl(-), and I(-) which are then used within Poisson-Boltzmann theory to calculate ionic distributions at surfaces of arbitrary charge for finite ion concentration. On the basis of calculated long-ranged electrostatic forces and coagulation properties, we obtain the direct anionic Hofmeister series at negatively charged hydrophobic surfaces. Reversal takes place when going to negative polar or to positive nonpolar surfaces, leading to the indirect series, while for positive polar surfaces the direct series is again obtained. This is in full accordance with a recent experimental classification of colloidal coagulation kinetics and also reflects the trends of the ion specific solubility properties of proteins. A schematic Hofmeister phase diagram is proposed. Partial series reversal is understood as a transient phenomenon for surfaces of intermediate polarity or charge.

The Link between Ion Specific Bubble Coalescence and Hofmeister Effects Is the Partitioning of Ions within the Interface

Specific ion effects are ubiquitous in soft matter systems and are most readily observed at high salt concentrations where long-range electrostatic forces are screened. In biological systems, ion-specificity is universal and is necessary to introduce the complexity required to carry out the processes of life. Many specific ion effects fall within the Hofmeister paradigm, whereby the strengths of action of the anions and cations follow a well-defined order, independent of the counterion. In contrast, specific ion effects evident in bubble coalescence inhibition depend on the combination of ions, and this phenomenon can be codified using simple ion-combining rules not evident in the Hofmeister systems. Here we show that these disparate specific ion effects have the same origin: They result from the variation in ion affinity for the solution interface. Equilibrium affinities explain Hofmeister effects, whereas we argue that the cation/anion combination controls bubble coalescence inhibition because of dynamic interfacial processes occurring at the more deformable gas-water interface.

First-principles modeling of ferroelectric capacitors via constrained displacement field calculations

First-principles modeling of ferroelectric capacitors presents several technical challenges, due to the coexistence of metallic electrodes, long-range electrostatic forces and short-range interface chemistry. Here we show how these aspects can be efficiently and accurately rationalized by using a finite-field density-functional theory formalism in which the fundamental electrical variable is the displacement field D. By performing calculations on model Pt/BaTiO3/Pt and Au/BaZrO3/Au capacitors we demonstrate how the interface-specific and bulk-specific properties can be identified and rigorously separated. Then, we show how the electrical properties of capacitors of arbitrary thickness and geometry (symmetric or asymmetric) can be readily reconstructed by using such information. Finally, we show how useful observables such as polarization and dielectric, piezoelectric and electrostrictive coefficients are easily evaluated as a byproduct of the above procedure. We apply this methodology to elucidate the relationship between chemical bonding, Schottky barriers and ferroelectric polarization at simple-metal/oxide interfaces. We find that BO2-electrode interfaces behave analogously to a layer of linear dielectric put in series with a bulk-like perovskite film, while a significant non-linear effect occurs at AO-electrode interfaces.

Electrochemical properties for ionic liquid/polymer electrolyte systems

The ionic liquid (1-ethyl-3-methylimidazolium hexafluorouphophate) ([emim][PF6]) with different molecular weights of poly(ethylene oxide) (PEO) (MW = 4600; 10,000; 14,000; 20,000; 35,000, and 100,000) has been characterized at various temperatures and compositions using phase behaviors and ionic conductivity. A molecular thermodynamic model based on a combination of the previous theory (BH model) by Chang et al., a nonrandomness theory (NR model), and the Pitzer-Debye-Hückel theory modified by Guggenheim (PDH model) considered not only short-range specific interactions between the polymer and a cation of the ionic liquid (IL), but also long-range electrostatic forces between anions and cations within the IL. We have derived a new melting point depression theory based on this BH-NR-PDH model. We also established an ionic conductivity model, based on the Nernst-Einstein equation, in which the diffusion coefficient is derived from the BH-NR-PDH model. The proposed model takes into account that the mobility of cations in the IL and the motions of the polymer host by expressing the effective chemical potential as the sum of the chemical potentials of the polymer and the IL. To describe the segmental motion of the cation and polymer chain, the effective coordinated unit parameter is introduced. The derived coordinated unit parameter for each state is used to determine the ionic conductivities of the given systems. Quantitative results from the proposed model are in good agreement with experimental data. The results indicate that the molecular weight of the polymer and the surrounding temperature play important roles in determining eutectic points and ionic conductivities of the given systems. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 212–219, 2010

The influence of surface topography on Kelvin probe force microscopy

Long-range electrostatic forces govern the imaging mechanism in electrostatic forcemicroscopy as well as in Kelvin probe force microscopy. To improve the analysis of suchimages, simulations of the electrostatic field distribution have been performed in the pastusing a flat surface and a cone-shaped tip. However, the electrostatic field distributionbetween a tip and a sample depends strongly on the surface topography, which has beenneglected in previous studies. It is therefore of general importance to study the influence ofsample topography features on Kelvin probe force microscopy images, which we addresshere by performing finite element simulations. We show how the surface potentialmeasurement is influenced by surface steps and surface grooves, considering potentialvariations in the form of a potential peak and a potential step. The influence of thetopography on the measurement of the surface potential is found to be rathersmall compared to a typical experimental resolution. Surprisingly, in the caseof a coinciding topography and potential step an improvement of the potentialprofile due to the inclusion of the topography is observed. Finally, based on theobtained results, suggestions for the realization of KPFM measurement are given.

Long-Ranged Attractive Forces Induced by Adsorbed Dendrimers: Direct Force Measurements and Computer Simulations

Interaction forces between charged interfaces in the presence of oppositely charged dendrimers are studied by experiment and simulation. The experiments involve direct force measurements with an atomic force microscope (AFM) between two negatively charged colloidal particles in the presence of adsorbed, positively charged globular dendrimers. The simulations are carried out by treating the macroions explicitly, while the small salt ions are treated implicitly through the Debye-Huckel approximation. The system undergoes overcharging, and at the isoelectric point long-ranged attractive electrostatic forces are present. The range of the attraction is on the order of half the Debye length at high salt concentration, but it becomes smaller at low salt concentration. Away from the isoelectric point, repulsive electrostatic forces are observed due to diffuse layer overlap. A semiquantitative agreement between experiment and simulation is obtained, despite the fact that the simple theoretical model does not involve any adjustable parameters. This study provides for the first time detailed comparison between experimental and simulation data of interaction forces between colloidal particles in the presence of multivalent macroions and monovalent salt ions.

An Implementation of the Smooth Particle Mesh Ewald Method on GPU Hardware.

The smooth particle mesh Ewald summation method is widely used to efficiently compute long-range electrostatic force terms in molecular dynamics simulations, and there has been considerable work in developing optimized implementations for a variety of parallel computer architectures. We describe an implementation for Nvidia graphical processing units (GPUs) which are general purpose computing devices with a high degree of intrinsic parallelism and arithmetic performance. We find that, for typical biomolecular simulations (e.g., DHFR, 26K atoms), a single GPU equipped workstation is able to provide sufficient performance to permit simulation rates of ≈50 ns/day when used in conjunction with the ACEMD molecular dynamics package (1) and exhibits an accuracy comparable to that of a reference double-precision CPU implementation.

The Role of Amphiphilicity and Negative Charge in Glycoprotein 41 Interactions in the Hydrophobic Pocket

The hydrophobic pocket within the coiled coil domain of HIV-1 gp41 is considered to be a hot-spot suitable for small molecule intervention of fusion, although so far it has yielded only microM inhibitors. Previous peptide studies have identified specific hydrophobic interactions and a Lys-Asp salt bridge as contributing to binding affinity in the pocket. Negative charge appears to be critical for activity of small molecules. We have examined the role of charge and amphiphilic character in the interaction by studying a series of short pocket binding peptides differing in charge, helical content, and in the presence or absence of the Lys-Asp salt bridge, and a series of fatty acid salts with varying charge and hydrocarbon length. Quantitative binding analysis revealed that long-range electrostatic forces and a greasy nonspecific hydrophobic interaction were sufficient for microM potency. The results suggest that an extended interaction site may be necessary for higher potency. We examined a region of the coiled coil immediately C-terminal to the pocket and found that specific salt bridge and hydrogen bond networks may reside in this region. Negatively charged groups extended toward or beyond the C-terminus of the pocket could therefore result in improved low molecular weight fusion inhibitors.

Diffuse interface field approach to modeling and simulation of self-assembly of charged colloidal particles of various shapes and sizes

A novel mesoscale simulation approach to modeling the collective interactions of charged colloidal particles allowing investigation of complex self-assembly processes is presented. Diffuse interface field variables are used to describe the shape, size, location and orientation of each individual particle within the computational domain. In addition, these field variables are used to determine the spatially resolved particle charge density distributions as well as the magnitude and direction of the electric field throughout the medium. Individual particle positions and rotations are updated in time as a result of long-range electrostatic and short-range repulsive forces and torques. Illustrative results of the model’s capability to evolve both monodisperse and binary distributions of charged particles of various shapes and charge characteristics are presented.