Electrostatic interaction in atomic force microscopy

In atomic force microscopy, the stylus experiences an electrostatic force when imaging in aqueous medium above a charged surface. This force has been calculated numerically with continuum theory for a silicon nitrite or silicon oxide stylus. For comparison, the Van der Waals force was also calculated. In contrast to the Van der Waals attraction, the electrostatic force is repulsive. At a distance of 0.5 nm the electrostatic force is typically 10^-12-10^-10 N and thus comparable in strength to the Van der Waals force. The electrostatic force increases with increasing surface charge density and decreases roughly exponentially with distance. It can be reduced by imaging in high salt concentrations. Below surface potentials of ≈50 mV, a simple analytical approximation of the electrostatic force is described.     

Equilibrium energy analysis of freeze-fracture planes in membranes

We have used equilibrium energy calculations to determine the most probable freeze-fracture planes in a lipid bilayer. Using a pairwise-summation computer method, we have generated numerical values for the Van der Waals potentials (electron shell repulsion, dispersion forces and electrostatic interactions) between molecules. We have compared our theoretical predictions with the experimental conclusion that the fracture planes occur normally between lipid molecules. These calculations also provide information about the composition of intramembranous particles, the potential for local clustering of single lipid types in the fluid membrane, and the importance of lipid molecules to the function of membrane proteins such as voltage-sensitive ion channels.     

Effect of branching in 4-alkylpyrazoles on liver alcohol dehydrogenase inhibition: A shape analysis study

Shape analysis methodology is applied to the study of 4-alkylpyrazoles which are known inhibitors of liver alcohol dehydrogenase. Elongation of the alkyl chain increases the inhibitory power, whereas branching of the chain diminishes the activity. These two counterpoised effects are studied simultaneously in a selected set of 4-alkylpyrazoles. A systematic conformational analysis followed by topological characterization of the van der Waals surfaces of all the local minima restricts the conformational space to potential bioactive structures. The analysis of the interrelation between the molecular electrostatic potential and van der Waals surfaces provides certain shape codes characteristic of each 4-alkylpyrazole. In both topological analyses van der Waals surfaces and molecular electrostatic potential van der Waals surface interrelations) graphical representations and analytical methods were used. A good correlation between the shape codes and the inhibitory activity is found for the linear derivatives. For branched pyrazoles, a tendency in their inhibitory power is predicted. Isopentylpyrazole is suggested to have the same inhibitory profile as 4-butylpyrazole, the linear derivative with one less carbon atom.     

Semi-empirical conformational analysis of propranolol interacting with dipalmitoylphosphatidylcholine

A semi-empirical conformational analysis is used to compute the conformation of (+)-propranolol inserted in dipalmitoylphosphatidylcholine. In a first step, the minimal conformational energy of the isolated molecule at the hydrocarbon-water interface is calculated as the sum of the contributions resulting from the Van der Waals, the torsional, the electrostatic and the transfer energies. Five pairs of conformers of minimal energy are determined. They are compared to data available from other experimental approaches. In a second step, they are assembled with dipalmitoylphosphatidylcholine at the interface. Although propranolol is considered in its protonated form, the electrostatic interaction with dipalmitoylphosphatidylcholine is negligible as compared to the Van der Waals interaction. The area occupied per propranolol molecule is between 0.53 and 0.64 nm2/molecule. In the most probable modes of insertion of propranolol into the lipid layer, the naphthyl moiety of the compound interacts with the lipid acyl chains. The protonated amino group is located in the vicinity of the phosphate residue possibly causing an electrostatic interaction.     

Theoretical studies of the electrostatic potential of some enzyme inhibitors using computer graphics techniques

A molecular graphics program is described for the depiction of electrostatic potentials on the van der Waals surface of molecules, using colored polygons. An example is given on the application of this method to the study of coumarins and flavones that inhibit the enzyme Glyoxalase I.     

基于遗传算法预测2D三向的蛋白质结构

本文基于范德华力势能预测2D三向的蛋白质结构。首先,将蛋白质结构预测这一生物问题转化为数学问题,并建立基于范德华力势能函数的数学模型。其次,使用遗传算法对数学模型进行求解,为了提高蛋白质结构预测效率,我们在标准遗传算法的基础上引入了调整算子这一概念,改进了遗传算法。最后,进行数值模拟实验。实验的结果表明范德华力势能函数模型是可行的,同时,和规范遗传算法相比,改进后的遗传算法能够较大幅度提高算法的搜索效率,并且遗传算法在蛋白质结构预测问题上有巨大潜力。     

On the relative importance of specific and non-specific approaches to oral microbial adhesion

Abstract In this paper, it is suggested that specificity and non-specificity in (oral) microbial adhesion are different expressions for the same phenomena. It is argued that the same basic, physico-chemical forces are responsible for so-called 'non-specific' and 'specific' binding and that from a physico-chemical point of view the distinction between the two is an artificial one. Non-specific interactions arise from Van der Waals and electrostatic forces and hydrogen bonding, and originate from the entire cell. A specific bond consists of a combination of the same type of Van der Waals and electrostatic forces and hydrogen bonding, now originating from highly localized chemical groups, which together form a stereo-chemical combination. The absence or presence of specific receptor sites on microbial cell surfaces must therefore be reflected in the overall, non-specific surface properties of cells as well. This point is illustrated by showing that glucanbinding lectins on mutans streptococcal strains may determine the pH dependence of the zeta potentials of these cells. When studying microbial adhesion, a non-specific approach may be better suited to explain adhesion to inert substrata, whereas a specific approach may be preferred in case of adhesion to adsorbed protein films. Adhesion is, however, not as important in plaque formation in the human oral cavity as is retention, because low shear force periods. during which adhesion presumably occurs, are followed by high shear force periods, during which adhering cells must withstand these detachment forces. Evidence is provided that such detachment will be through cohesive failure in the pellicle mass, the properties of which are conditioned by the overall, non-specific substratum properties. Therefore, in vivo plaque formation may be more readily explained by a non-specific approach.     

The adhesion of pathogenic microflora on carbon sorbents

The adsorbing activity of granulated carbonic sorbents SKN and KAU, as well as their oxidated forms, containing protogenic carboxylic and phenolic groups with respect to Shigella flexneri, Salmonella typhimurium, Escherichia coli, Streptococcus aureus and Pseudomonas aeruginosa pathogenic strains has been studied. As shown in this study, the process of interaction between microorganisms and carbonic sorbents has two stages. At the first stage the main role is played by long-distance electrostatic forces and at the second stage, by Van der Waals short-distance forces, as well as bonds formed between cell structures and surface groupings of carbonaceous materials. In the mechanism of interaction between microbial cells and carbons the geometry of carbon surface plays an important role. KAU(0)-1 exhibits the highest degree of adhesion with respect to pathogenic bacteria.     

Molecular dynamics of phenylalanine transfer RNA

The atomic motions of yeast phenylalanine transfer RNA have been simulated using the molecular dynamics algorithm. Two simulations were carried out for a period of 12 picoseconds, one with a normal Van der Waals potential and the other with a modified Van der Waals potential intended to mimic the effect of solvent. An analysis of large scale motions, surface exposure, root mean square displacements, helical oscillations and relaxation mechanisms reveals the maintenance of stability in the simulated structures and the general similarity of the various dynamic features of the two simulations. The regions of conformational flexibility and rigidity for tRNA(Phe) have been shown in a quantitative measure through this approach.     

On the relative importance of specific and non-specific approaches to oral microbial adhesion.

In this paper, it is suggested that specificity and non-specificity in (oral) microbial adhesion are different expressions for the same phenomena. It is argued that the same basic, physicochemical forces are responsible for so-called 'non-specific' and 'specific' binding and that from a physico-chemical point of view the distinction between the two is an artificial one. Non-specific interactions arise from Van der Waals and electrostatic forces and hydrogen bonding, and originate from the entire cell. A specific bond consists of a combination of the same type of Van der Waals and electrostatic forces and hydrogen bonding, now originating from highly localized chemical groups, which together form a stereochemical combination. The absence or presence of specific receptor sites on microbial cell surfaces must therefore be reflected in the overall, non-specific surface properties of cells as well. This point is illustrated by showing that glucan-binding lectins on mutans streptococcal strains may determine the pH dependence of the zeta potentials of these cells. When studying microbial adhesion, a non-specific approach may be better suited to explain adhesion to inert substrata, whereas a specific approach may be preferred in case of adhesion to adsorbed protein films. Adhesion is, however, not as important in plaque formation in the human oral cavity as is retention, because low shear force periods, during which adhesion presumably occurs, are followed by high shear force periods, during which adhering cells must withstand these detachment forces. Evidence is provided that such detachment will be through cohesive failure in the pellicle mass, the properties of which are conditioned by the overall, non-specific substratum properties. Therefore, in vivo plaque formation may be more readily explained by a non-specific approach.     

DFT study of water adsorption on lignite molecule surface

High moisture content is a main characteristic of low-rank coal, such as lignite. Numerous oxygen containing functional groups in lignite make it represent some special properties, and these functional groups affect the adsorption mechanisms of water molecules on lignite surface. This study reports some typical water?·?·?·?lignite conformations, along with a detailed analysis of the geometry, electrostatic potential distribution, reduced density gradient of interaction, and interaction energy decomposition. The results show that water molecules tend to aggregate around functional groups, and hydrogen bonds play a dominant role in the interaction. The adsorption energy of water cluster on lignite surface is larger than that of isolated water molecule, a good linear relationship between the interaction distance and adsorption energy of layers has been found. Since water is a polar molecule, the local minima and maxima of electrostatic potential in conformations increase along with more water adsorbing on lignite surface. Reduced density gradient analysis shows that H-bonds, van der Waals interaction, and a little steric make up the interaction between water cluster and lignite molecule. In these studied conformations which mainly are H-bond complexes, electrostatic and exchange repulsion play a dominant role, whereas polarization and dispersion make relatively small contribution to the interaction. Attractive and repulsive interaction both affect the stability of water?·?·?·?lignite conformations.     

Estimation of the binding affinities of FKBP12 inhibitors using a linear response method.

A series of non-immunosuppressive inhibitors of FK506 binding protein (FKBP12) are investigated using Monte Carlo statistical mechanics simulations. These small molecules may serve as scaffolds for chemical inducers of protein dimerization, and have recently been found to have FKBP12-dependent neurotrophic activity. A linear response model was developed for estimation of absolute binding free energies based on changes in electrostatic and van der Waals energies and solvent-accessible surface areas, which are accumulated during simulations of bound and unbound ligands. With average errors of 0.5 kcal/mol, this method provides a relatively rapid way to screen the binding of ligands while retaining the structural information content of more rigorous free energy calculations.     

Prediction of inhibitor binding free energies by quantum neural networks. Nucleoside analogues binding to trypanosomal nucleoside hydrolase

A computational method has been developed to predict inhibitor binding energy for untested inhibitor molecules. A neural network is trained from the electrostatic potential surfaces of known inhibitors and their binding energies. The algorithm is then able to predict, with high accuracy, the binding energy of unknown inhibitors. IU-nucleoside hydrolase from Crithidia fasciculata and the inhibitor molecules described previously [Miles, R. W. Tyler, P. C. Evans, G. Furneaux R. H., Parkin, D. W., and Schramm, V. L. (1999) Biochemistry 38, xxxx-xxxx] are used as the test system. Discrete points on the molecular electrostatic potential surface of inhibitor molecules are input to neural networks to identify the quantum mechanical features that contribute to binding. Feed-forward neural networks with back-propagation of error are trained to recognize the quantum mechanical electrostatic potential and geometry at the entire van der Waals surface of a group of training molecules and to predict the strength of interactions between the enzyme and novel inhibitors. The binding energies of unknown inhibitors were predicted, followed by experimental determination of K(i)() values. Predictions of K(i)() values using this theory are compared to other methods and are more robust in estimating inhibitory strength. The average deviation in estimating K(i)() values for 18 unknown inhibitor molecules, with 21 training molecules, is a factor of 5 x K(i)() over a range of 660 000 in K(i)() values for all molecules. The a posteriori accuracy of the predictions suggests the method will be effective as a guide for experimental inhibitor design.     

Hydrophobicity at the surface of proteins

A new method is presented to quantitatively estimate and graphically display the propensity of nonpolar groups to bind at the surface of proteins. It is based on the calculation of the binding energy, i.e., van der Waals interaction plus protein electrostatic desolvation, of a nonpolar probe sphere rolled over the protein surface, and on the color coding of this quantity on a smooth molecular surface (hydrophobicity map). The method is validated on ten protein-ligand complexes and is shown to distinguish precisely where polar and nonpolar groups preferentially bind. Comparisons with existing approaches, like the display of the electrostatic potential or the curvature, illustrate the advantages and the better predictive power of the present method. Hydrophobicity maps will play an important role in the characterization of binding sites for the large number of proteins emerging from the genome projects and structure modeling approaches.     

Molecular Dynamics of Phenylalanine Transfer RNA

Abstract

The atomic motions of yeast phenylalanine transfer RNA have been simulated using the molecular dynamics algorithm. Two simulations were carried out for a period of 12 picoseconds, one with a normal Van der Waals potential and the other with a modified Van der Waals potential intended to mimic the effect of solvent. An analysis of large scale motions, surface exposure, root mean square displacements, helical oscillations and relaxation mechanisms reveals the maintenance of stability in the simulated structures and the general similarity of the various dynamic features of the two simulations. The regions of conformational flexibility and rigidity for tRNA^Phe have been shown in a quantitative measure through this approach.     

Prediction of Protein Binding to DNA in the Presence of Water-Mediated Hydrogen Bonds

We extend our previous analysis of binding specificity of DNA-protein complexes to complexes containing water-mediated bridges. Inclusion of water bridges between phosphate and base, phosphate and sugar, as well as proteins and DNA, improves the prediction of specificity; six data sets studied in this paper yield correct predictions for all base pairs that have two or more hydrogen-bonds. Beside massive computation, our approach relies highly on experimental data. After deriving protein structures from DNA-protein complexes in which coordinates were established by X-ray diffraction techniques, we analysed all possible DNA sequences to which these proteins might bind, ranking them in terms of Lennard-Jones potential for the optimal docking configuration. Our prediction algorithm rests on the following assumptions: (1) specificity comes mainly from direct hydrogen bonding; (2) electrostatic forces stabilise DNA-protein complexes and contribute only weakly to specificity since they occur at the charged phosphate groups; (3) Van der Waals forces and electrostatic interactions between positively charged groups on the protein and phosphates on DNA can be neglected as they contribute primarily to the free energy of stabilisation as opposed to specificity.     

Mode of insertion of chlorophyll a in a lipid layer. A conformational approach

A new procedure for conformational analysis is described to define the orientation of chlorophyll a in model membranes. The method allows to predict the configuration of assembled amphiphilic molecules. The minimal conformational energy is calculated as the sum of the contributions, resulting from the Van der Waals interactions, the torsional potentials, the electrostatic interactions and the transfer energy. In the calculated conformation, the porphyrin ring is orientated at an angle of 45° ± 5° to the membrane interface, with the phytol chain inserted into the lipid layer. This orientation of the porphyrin ring is in excellent agreement with the experimental value obtained with model membranes. The method could allow to define the orientation of other components in the thylakoid membrane.     

Phenomenon of Quantum Entanglement in a System Composed of Two Minimal Protocells

The quantum mechanical self-assembly of two separate photoactive supramolecular systems with different photosynthetic centers was investigated by means of density functional theory methods. Quantum entangled energy transitions from one subsystem to the other and the assembly of logically controlled artificial minimal protocells were modeled. The systems studied were based on different photoactive sensitizer molecules covalently bonded to a non-canonical oxo-guanine::cytosine supramolecule with the precursor of a fatty acid (pFA) molecule attached via Van der Waals forces, all surrounded by water molecules. The electron correlation interactions responsible for the weak hydrogen and Van der Waals chemical bonds increased due to the addition of polar water solvent molecules. The distances between the separated sensitizer, nucleotide, pFA, and water molecules are comparable to Van der Waals and hydrogen bonding radii. As a result, the overall system becomes compressed, resulting in photo-excited electron tunneling from the sensitizer (bis(4-diphenylamine-2-phenyl)-squarine or 1,4-bis(N,N-dimethylamino)naphthalene) to the pFA molecules. Absorption spectra as well as electron transfer trajectories associated with the different excited states were calculated using time dependent density functional theory methods. The results allow separation of the quantum entangled photosynthetic transitions within the same minimal protocell and with the neighboring minimal protocell. The transferred electron is used to cleave a “waste” organic molecule resulting in the formation of the desired product. A two variable, quantum entangled AND logic gate was proposed, consisting of two input photoactive sensitizer molecules and one output (pFA molecule). It is proposed that a similar process might be applied for the destruction of tumor cancer cells or to yield building blocks in artificial cells.