Normal mode analysis and applications in biological physics.

Normal mode analysis has become a popular and often used theoretical tool in the study of functional motions in enzymes, viruses, and large protein assemblies. The use of normal modes in the study of these motions is often extremely fruitful since many of the functional motions of large proteins can be described using just a few normal modes which are intimately related to the overall structure of the protein. In this review, we present a broad overview of several popular methods used in the study of normal modes in biological physics including continuum elastic theory, the elastic network model, and a new all-atom method, recently developed, which is capable of computing a subset of the low frequency vibrational modes exactly.

Atomistic modeling of the low-frequency mechanical modes and Raman spectra of icosahedral virus capsids.

We describe a technique for calculating the low-frequency mechanical modes and frequencies of a large symmetric biological molecule where the eigenvectors of the Hessian matrix are determined with full atomic detail. The method, which follows order N methods used in electronic structure theory, determines the subset of lowest-frequency modes while using group theory to reduce the complexity of the problem. We apply the method to three icosahedral viruses of various T numbers and sizes; the human viruses polio and hepatitis B, and the cowpea chlorotic mottle virus, a plant virus.

Photonic approach to the selective inactivation of viruses with a near-infrared subpicosecond fiber laser.

We report a photonic approach for selective inactivation of viruses with a near-infrared subpicosecond laser. We demonstrate that this method can selectively inactivate viral particles ranging from nonpathogenic viruses such as the M13 bacteriophage and the tobacco mosaic virus to pathogenic viruses such as the human papillomavirus and the human immunodeficiency virus (HIV). At the same time, sensitive materials such as human Jurkat T cells, human red blood cells, and mouse dendritic cells remain unharmed.

Vibrational energy funneling in viruses-simulations of impulsive stimulated Raman scattering in M13 bacteriophage.

The vibrational excitation of a tubular M13 bacteriophage capsid is simulated using classical molecular dynamics. The excitation occurs through impulsive stimulated Raman scattering by ultra-short laser pulses which ping the vibrational modes of the capsid. Tuning the laser pulse temporal width determines the frequency region of the capsid that is excited.

Simulations of impulsive laser scattering of biological protein assemblies: application to M13 bacteriophage.

We develop a theoretical framework, based on a bond-polarizability model, for simulating the impulsive force experienced on a protein or an assembly of proteins from a pulsed light source by coupling the laser electric field to an atomic distortion. The mechanism is impulsive stimulated Raman scattering (ISRS) where mechanical distortions produce variation in the electronic polarization through atomic displacements similar to vibrational Raman scattering. The magnitude of the impulsive force is determined from the empirical two-body bond-polarizability model and the intensity of the incident light.

Insights into electron tunneling across hydrogen-bonded base-pairs in complete molecular circuits for single-stranded DNA sequencing.

We report a first-principles study of electron ballistic transport through a molecular junction containing deoxycytidine-monophosphate (dCMP) connected to metal electrodes. A guanidinium ion and guanine nucleobase are tethered to gold electrodes on opposite sides to form hydrogen bonds with the dCMP molecule providing an electric circuit. The circuit mimics a component of a potential device for sequencing unmodified single-stranded DNA.

Theory of tunneling across hydrogen-bonded base pairs for DNA recognition and sequencing.

We present the results of first-principles calculations for the electron tunnel current through hydrogen-bonded DNA base pairs and for (deoxy)nucleoside-nucleobase pairs. Electron current signals either through a base pair or through a deoxynucleoside-nucleobase pair are a potential mechanism for recognition or identification of the DNA base on a single-stranded DNA polymer. Four hydrogen-bonded complexes are considered: guanine-cytosine, diaminoadenine-thymine, adenine-thymine, and guanine-thymine.

Structural and dynamic properties of BaInGeH: a rare solid-state indium hydride.

BaInGeH was synthesized by hydrogenating the intermetallic compound BaInGe. The crystal structure determination from the powder neutron diffraction data of BaInGeD [P3m1, Z = 1, a = 4.5354(3) A, c = 5.

A hydrogen-bonded electron-tunneling circuit reads the base composition of unmodified DNA.

Using a tunnel junction in which one electrode is guanidinium-functionalized (to trap DNA via hydrogen bonding to the backbone phosphates) and a second electrode which is functionalized with a base (to capture its complementary target on the DNA), current versus distance curves are obtained which yield an accurate measure of the base composition of DNA oligomers. With this long tunneling path, resolution is limited to sequence blocks of about twenty bases or larger, because of the need to form a large-area tunnel junction. A shorter hydrogen-bonded path across bases will be required for DNA sequencing.

Theory of the low frequency mechanical modes and Raman spectra of the M13 bacteriophage capsid with atomic detail.

We present a theoretical study of the low frequency vibrational modes of the M13 bacteriophage using a fully atomistic model. Using ideas from electronic structure theory, the few lowest vibrational modes of the M13 bacteriophage are determined using classical harmonic analysis. The relative Raman intensity is estimated for each of the mechanical modes using a bond polarizability model.

Vibrational property study of SrGa2H2 and BaGa2H2 by inelastic neutron scattering and first principles calculations.

Vibrational properties of the gallium hydrides SrGa2H2 and BaGa2H2 have been investigated by means of inelastic neutron scattering (INS) and first-principles calculations. The compounds contain Ga-H units being part of a two-dimensional polyanionic layer, [(GaH)(GaH)]2-. The INS spectra are composed of dispersed internal Ga-H bending and stretching modes at frequencies above 600 cm(-1) and external lattice modes at frequencies below 220 cm(-1).

Low frequency mechanical modes of viral capsids: an atomistic approach.

We present a method for the calculation of the low frequency vibrational modes and frequencies of viral capsids, or other large molecules, where the modes are modeled with atomic detail. Extending ideas from electronic structure theory, an energy functional is used to find modes of a classical dynamical matrix below a fixed (pseudo-Fermi) level. The icosahedral satellite tobacco necrosis virus is modeled as an example.

Raman intensity and spectra predictions for cylindrical viruses.

A theoretical framework for predicting low frequency Raman vibrational spectra of viral capsids is presented and applied to the M13 bacteriophage. The method uses a continuum elastic theory for the vibrational modes and a bond-charge polarizability model of an amorphous material to roughly predict the Raman intensities. Comparison is made to experimental results for the M13 bacteriophage virus.

Vibrational properties of polyanionic hydrides SrAl2H2 and SrAlSiH: new insights into Al-H bonding interactions.

The vibrational properties of the recently discovered aluminum hydrides SrAl2H2 and SrAlSiH have been investigated by means of inelastic neutron scattering (INS) and first-principles calculations. Both compounds contain Al-H units being part of a two-dimensional polyanionic layer, [(AlH)(AlH)]2- and [Si(AlH)]2-, respectively. The INS spectrum of SrAlSiH is characterized by very weakly dispersed Al-H modes with well-resolved overtones, while SrAl2H2 yields a solid-state dispersed phonon spectrum.

Probing the low-frequency vibrational modes of viruses with Raman scattering--bacteriophage M13 in water.

Raman spectroscopy is used to study low-wave-number ( View Article and Find Full Text PDF

Observation of the low frequency vibrational modes of bacteriophage M13 in water by Raman spectroscopy.

Background: Recently, a technique which departs radically from conventional approaches has been proposed. This novel technique utilizes biological objects such as viruses as nano-templates for the fabrication of nanostructure elements. For example, rod-shaped viruses such as the M13 phage and tobacco mosaic virus have been successfully used as biological templates for the synthesis of semiconductor and metallic nanowires.

Holliday junction dynamics and branch migration: single-molecule analysis.

The Holliday junction (HJ) is a central intermediate in various genetic processes including homologous and site-specific recombination and DNA replication. Branch migration allows the exchange between homologous DNA regions, but the detailed mechanism for this key step of DNA recombination is unidentified. Here, we report direct real-time detection of branch migration in individual molecules.

Conduction switching of photochromic molecules.

We report a theoretical study of single molecule conduction switching of photochromic dithienylethene molecules. The light-induced intramolecular transformation drives a swapping of the highest occupied molecular orbital and lowest unoccupied molecular orbital between two distinct conjugated paths. The shuffling of single and double bonds produces a significant conductance change when the molecule is sandwiched between metal electrodes.

Electronic decay constant of carotenoid polyenes from single-molecule measurements.

The conductance of carotenoid polyenes chemically bound at each end to gold contacts has been measured for single molecules containing 5, 7, 9, and 11 carbon-carbon double bonds in conjugation. The electronic decay constant, beta, is determined to be 0.22 +/- 0.

Band-gap tunneling states in DNA.

An important issue regarding DNA electrical conductivity is the electron (hole) transfer rate. Experiments have found that this transfer rate involves quantum mechanical tunneling for short distances and thermally activated hopping over large distances. The electron (or hole) tunneling probability through a molecule depends on the length of molecule L, as e(-beta(E)L), where the tunneling betaE factor is strongly energy dependent.

Supercoiling-induced DNA bending.

Local DNA bending is a critical factor for numerous DNA functions including recognition of DNA by sequence-specific regulatory binding proteins. Negative DNA supercoiling increases both local and global DNA dynamics, and this dynamic flexibility can facilitate the formation of DNA-protein complexes. We have recently shown that apexes of supercoiled DNA molecules are sites that can promote the formation of an alternative DNA structure, a cruciform, suggesting that these positions in supercoiled DNA are under additional stress and perhaps have a distorted DNA geometry.

Theoretical analysis of electron transport through organic molecules.

We present a theoretical study of electron transport through a variety of organic molecules. The analysis uses the Landauer formalism in combination with complex bandstructure and projected densities of states calculations to reveal the main aspects of coherent electronic transport through alkanes, benzene-dithiol, and phenylene-ethynylene oligomers. We examine the dependence of the current on molecule length, the effects of molecule-molecule interactions from film packing, differences in contact geometry, and the influence of phenyl ring rotation on the conductances of phenylene-ethynylene oligomers such as 1,4-bis-phenylethynyl-benzene.

Influence of global DNA topology on cruciform formation in supercoiled DNA.

DNA supercoiling plays an important role in many genetic processes such as replication, transcription, and recombination. Supercoiling provides energy for helix un-pairing and drives the formation of alternative DNA structural transitions, like cruciforms. Supercoiling also allows distant DNA regions to be brought into close proximity through the formation of inter-wound supercoils.

Bias-induced forces in conducting atomic force microscopy and contact charging of organic monolayers.

Contact electrification, a surface property of bulk dielectric materials, has now been observed at the molecular scale using conducting atomic force microscopy (AFM). Conducting AFM measures the electrical properties of an organic film sandwiched between a conducting probe and a conducting substrate. This paper describes physical changes in the film caused by the application of a bias.

Reproducible measurement of single-molecule conductivity.

A reliable method has been developed for making through-bond electrical contacts to molecules. Current-voltage curves are quantized as integer multiples of one fundamental curve, an observation used to identify single-molecule contacts. The resistance of a single octanedithiol molecule was 900 +/- 50 megohms, based on measurements on more than 1000 single molecules.