The beauty of molecular surfaces as revealed by self-organizing neural networks

The Kohonen neural network is a self-organizing network that can be used for the projection of the surface properties of molecules. This allows one to view properties on a molecular surface, like the electrostatic potential in a single picture. These maps are useful for the comparison of molecules and provide a new definition of molecular similarity.     

SMILE-shaded molecular imaging on low-cost equipment

The SMILE program runs under MS-DOS on IBM PC AT-compatible computers equipped with the SM640 or the PG640 Matrox graphic board. The program allows real-time three-dimensional (3D) animation and modeling of several isolated molecules that can be built from scratch, manipulated interactively and compared by superimposition.SMILE enables users to compute atomic partial charges, molecular surface area, molecular volume, electrostatic and nonbonded potential energies. PLUTO, ORTEP, and MMP2 input files are set up automatically. The program also provides simple access to crystal packing by real-time animation of the unit cell contents, interactive inspection of the relevant stereochemical parameters and fragment manipulation within the unit cell. SMILE animates stereo views and produces beautiful shaded 3D images (8 colors, 32 shades each) of molecules in many different styles—stick, ball-and-stick, CPK (space filling), and transparent CPK with backbone.     

Internal water molecules and H-bonding in biological macromolecules: a review of structural features with functional implications.

Conserved structural patterns of internal water molecules and/or H-bond chains were observed and are here correlated in this review, which then describes two functional properties: equilibration of hydrostatic pressure and proton transport. Available evidence in support of these hypotheses is presented, together with suggested experiments to test them. High-resolution crystal structures of a variety of proteins were studied with interactive computer graphics. Conserved H-bonding linkages may be used as a paradigm for a rationalization of proton transport in membranes. The concept of the "proton wire," which links buried active-site amino acids with the surface of the protein raises the more general question of the functional role of the various molecular components.     

Evanescent Field Based Photoacoustics: Optical Property Evaluation at Surfaces

Here, we present a protocol to estimate material and surface optical properties using the photoacoustic effect combined with total internal reflection. Optical property evaluation of thin films and the surfaces of bulk materials is an important step in understanding new optical material systems and their applications. The method presented can estimate thickness, refractive index, and use absorptive properties of materials for detection. This metrology system uses evanescent field-based photoacoustics (EFPA), a field of research based upon the interaction of an evanescent field with the photoacoustic effect. This interaction and its resulting family of techniques allow the technique to probe optical properties within a few hundred nanometers of the sample surface. This optical near field allows for the highly accurate estimation of material properties on the same scale as the field itself such as refractive index and film thickness. With the use of EFPA and its sub techniques such as total internal reflection photoacoustic spectroscopy (TIRPAS) and optical tunneling photoacoustic spectroscopy (OTPAS), it is possible to evaluate a material at the nanoscale in a consolidated instrument without the need for many instruments and experiments that may be cost prohibitive.     

Approximation and visualization of large-scale motion of protein surfaces

We present a method for the approximation and real-time visualization of large-scale motion of protein surfaces. A molecular surface is represented by an expansion of spherical harmonic functions, and the motion of protein atoms around their equilibrium positions is computed by normal mode analysis. The motion of the surface is approximated by projecting the normal mode vectors of the solvent-accessible atoms to the spherical harmonic representation of the molecular surface. These surface motion vectors are represented by a separated spherical harmonic expansion. Representing the surface geometry and the surface motion vectors by spherical harmonic expansions allows variable-resolution analysis and real-time display of the large-scale surface motion. This technique has been applied to interactive visualization, interactive surface manipulation, and animation.     

Hydrodynamic properties of DNA and DNA-lipid complex in an elongational flow field

The aim of this study was to determine the difference between hydrodynamic properties of DNA-cetyltrimethylammonium (CTA) complex and those of DNA, which may be related to the difference in fibre-forming ability of DNA-CTA from that of DNA. Responses of DNA and DNA-CTA complex to an elongational flow field were investigated. In both solution systems, results suggesting a coil-stretch transition were obtained. From a critical strain rate value, the radius of gyration of DNA-CTA molecules in ethanol-glycerol solution was revealed to be 0.3-0.5 times of that of DNA in aqueous NaCl solution. Shear viscosity of DNA-CTA solution was much smaller than that of DNA solution, also suggesting a smaller size of DNA-CTA in ethanol-glycerol solution than that of DNA in aqueous NaCl solution. The plateau birefringence value of the DNA-CTA system, a parameter that indicates the local molecular conformation and the molecular arrangement, was only about 1/10 of that of the DNA system. There is an empirically determined molecular model of DNA-CTA complex in which a DNA molecule is sheathed by a cylindrical crust made of CTA chains. This structure reduces the DNA molecular density in a pure elongational flow field region but cannot explain the observed reduction of birefringence intensity. The small plateau birefringence value of DNA-CTA compared with that of DNA was attributed to the reduced molecular polarizability by the particular conformation of DNA molecules and CTA chains in the DNA-CTA system such as that expected by the conformational models.     

Investigating protein-protein interaction surfaces using a reduced stereochemical and electrostatic model

A method of calculating the electrostatic potential energy between two molecules, using finite difference potential, is presented. A reduced charge set is used so that the interaction energy can be calculated as the two static molecules explore their full six-dimensional configurational space. The energies are contoured over surfaces fixed to each molecule with an interactive computer graphics program. For two crystal structures (trypsin-trypsin inhibitor and anti-lysozyme Fab-lysozyme), it is found that the complex corresponds to highly favourable interacting regions in the contour plots. These matches arise from a small number of protruding basic residues interacting with enhanced negative potential in each case. The redox pair cytochrome c peroxidase-cytochrome c exhibits an extensive favourably interacting surface within which a possible electron transfer complex may be defined by an increased electrostatic complementarity, but a decreased electrostatic energy. A possible substrate transfer configuration for the glycolytic enzyme pair glyceraldehyde phosphate dehydrogenase-phosphoglycerate kinase is presented.     

Lipophilicity force field profile: An expressive visualization of the lipophilicity molecular potential gradient

This paper proposes a new tool that allows us to see the following in the same frame: (1) 3D geometrical features of a molecule, and (2) pseudo-3D representation of the lipohilicity molecular potential. It thus becomes very easy to compare the lipohilicity molecular potential gradient of different molecules having the same pharmacological properties. An example of two structurally dissimilar anti-PAF molecules is given.     

Endothelial glycocalyx of blood circulation system. I. Detection,components, and structural organization

The luminal surface of a blood vessel accommodates a complex multicomponent system of mainly carbohydrates and proteins called glycocalyx. According to the concept of the double protective layer, glycocalyx is the first protection barrier of the vascular wall. The structure of glycocalyx is determined by a group of proteoglycans, glycoproteins, and glycosaminoglycans. Two groups of molecules are distinguished within the glycocalyx constituents, that is, membrane proteoglycans (syndecans and glypicans bound to endothelial cell membranes) and soluble proteoglycans (perlecan, biglycan, versican, decorin, and mimecan). There are five types of glycosaminoglycan chains; these are heperan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronan. There is a dynamic equilibrium between the soluble components of glycocalyx and flowing blood, which allows for separation of the endothelial surface layer. Due to its complexity and location at the interface of blood circulation system, glycocalyx is involved in the maintenance of vascular homeostasis. Here, the molecular composition of glycocalyx, properties of its components, biosynthesis, and common structural features are discussed.     

Dynamic molecules: molecular dynamics for everyone. An internet-based access to molecular dynamic simulations: basic concepts

Molecular dynamics is a rapidly developing field of science and has become an established tool for studying the dynamic behavior of biomolecules. Although several high quality programs for performing molecular dynamic simulations are freely available, only well-trained scientists are currently able to make use of the broad scientific potential that molecular dynamic simulations offer to gain insight into structural questions at an atomic level. The "Dynamic Molecules" approach is the first internet portal that provides an interactive access to set up, perform and analyze molecular dynamic simulations. It is completely based on standard web technologies and uses only publicly available software. The aim is to open molecular dynamics techniques to a broader range of users including undergraduate students, teachers and scientists outside the bioinformatics field. The time-limiting factors are the availability of free capacity on the computing server to run the simulations and the time required to transport the history file through the internet for the animation mode. The interactive access mode of the portal is acceptable for animations of molecules having up to about 500 atoms.Figure Several main menus (see top) are provided to start "New Simulations", to "Display Simulations" and to "Analyze" statistical and geometrical properties of the molecule. Here the "Display Simulation" interface is shown. The Chime plugin is used to visualize molecular 3D structures and motions.     

Program for the visualization and interactive study of molecules on a calligraphic display system

Mops is a computer program for the visualization and interactive analysis of crystallographic and molecular structures on a calligraphic PS 300 display system. This system allows the interactive display of bond lengths, bond angles and torsion angles with colour coding of atom types as well as crystalline packing interactions. Mops is also capable of easily drawing a chosen image on the screen using the Ortep program. This facility allows the very fast preparation of slides or illustrations.     

"DNA-Dressed NAnopore" for complementary sequence detection

Single molecule electrical sensing with nanopores is a rapidly developing field with potential revolutionary effects on bioanalytics and diagnostics. The recent success of this technology is in the simplicity of its working principle, which exploits the conductance modulations induced by the electrophoretic translocation of molecules through a nanometric channel. Initially proposed as fast and powerful tools for molecular stochastic sensing, nanopores find now application in a range of different domains, thanks to the possibility of finely tuning their surface properties, thus introducing artificial binding and recognition sites. Here we show the results of DNA translocation and hybridization experiments at the single molecule level by a novel class of selective biosensor devices that we call "DNA-Dressed NAnopore" (DNA(2)), based on solid state nanopore with large initial dimensions, resized and activated by functionalization with DNA molecules. The presented data demonstrate the ability of the DNA(2) to selectively detect complementary target sequences, that is to distinguish between molecules depending on their affinity to the functionalization. The DNA(2) can thus constitute the basis for the design of integrable parallel devices for mutation DNA analysis, diagnostics and bioanalytic investigations.     

Glycans and neural cell interactions

Carbohydrate-carrying molecules in the nervous system have important roles during development, regeneration and synaptic plasticity. Carbohydrates mediate interactions between recognition molecules, thereby contributing to the formation of a complex molecular meshwork at the cell surface and in the extracellular matrix. The tremendous structural diversity of glycan chains allows for immense combinatorial possibilities that might underlie the fine-tuning of cell-cell and cell-matrix interactions.     

Atomic force bio-analytics

The atomic force microscope (AFM) allows biomolecules to be observed and manipulated under native conditions. It operates in buffer solution, produces molecular images with outstanding signal-to-noise ratio, and addresses single molecules. Progress in sample preparation and instrumentation has led to topographs that reveal sub-nanometer details and surface dynamics of biomolecules. Antibodies or oligonucleotides immobilized on cantilevers induce bending upon binding of the cognate biomolecule, allowing sub-picomolar concentrations to be measured. Biomolecules tethered between support and retracting AFM-tip produce force extension curves that reflect the mechanical stability of secondary structure elements. Furthermore, multifunctional tips may activate single molecules to observe them at work. In all cases, the cantilever is critical: its mechanical properties dictate the force-sensitivity and the scanning speed.     

Molecular-dynamic simulation of phospholipid bilayers: Ion distribution at the surface of neutral and charged bilayer in the liquid crystalline state

The electric field and ion distribution at the surface of neutral and charged lipid bilayers (BeCl₂ and dipalmitoyl phosphatidylcholine/dipalmitoyl phosphatidylserine (DPPC/DPPS) + KCl) were studied with molecular dynamic (MD) methods. It is shown that the contributions of lipid molecules, water and ions to the electric potential compensate each other in the region of the diffuse double layer and decrease the potential value close to zero. It is also demonstrated that the ion distribution at the charged surface is determined not only by the electrostatic ion-medium interaction. The total energy of this interaction was compared with the potential of mean ion force. It was shown that cations and anions have a different effect on the state of water molecules at the surface. The order parameter of water in the system DPPC + BeCl₂ and the Clion distribution have the extremum at the distance of 10 α atoms of the phospholipid glycerol. This position was chosen as the “electrical” interface of the electrical double layer (EDL) for all lipid systems studied. The potential of mean force of counter ions in EDL allows us to obtain the value of potential at the lipid surface suitable for experimental test of the MD data. This surface potential and surface charge density was found from MD simulation different electrolyte concentrations and DPPS content of 20, 40 and 60% in the mixture with DPPC and was shown to be in a good agreement with the Gouy-Chapman-Stern model upon fitting parameters close to their experimental values.     

Quantitative characterization of agglomerates and aggregates of pyrogenic and precipitated amorphous silica nanomaterials by transmission electron microscopy

ABSTRACT: BACKGROUND: The interaction of a nanomaterial (NM) with a biological system depends not only on the sizeof its primary particles but also on the size, shape and surface topology of its aggregates andagglomerates. A method based on transmission electron microscopy (TEM), to visualize theNM and on image analysis, to measure detected features quantitatively, was assessed for itscapacity to characterize the aggregates and agglomerates of precipitated and pyrogenicsynthetic amorphous silicon dioxide (SAS), or silica, NM. RESULTS: Bright field (BF) TEM combined with systematic random imaging and semi-automatic imageanalysis allows measuring the properties of SAS NM quantitatively. Automation allows measuring multiple and arithmetically complex parameters simultaneously on high numbersof detected particles. This reduces operator-induced bias and assures a statistically relevantnumber of measurements, avoiding the tedious repetitive task of manual measurements.Access to multiple parameters further allows selecting the optimal parameter in function of aspecific purpose.Using principle component analysis (PCA), twenty-three measured parameters wereclassified into three classes containing measures for size, shape and surface topology of theNM. CONCLUSION: The presented method allows a detailed quantitative characterization of NM, like dispersionsof precipitated and pyrogenic SAS based on the number-based distributions of their meandiameter, sphericity and shape factor.