Ideas in theoretical biology

The potential and realized impact of Bohm's views on biology are briefly discussed.     

A small protein in model membranes: a time-resolved fluorescence and ESR study on the interaction of M13 coat protein with lipid bilayers

Model membranes with unsaturated lipid chains containing various amounts of M13 coat protein in the -helical form were studied using time-resolved fluorescence and ESR spectroscopy. The lipid-to-protein (L/P) ratios used were > 12 to avoid protein-protein contacts and irreversible aggregation leading to -polymeric coat protein. In the ESR spectra of the 12-SASL probe in dioleoyl phosphatidylcholine (DOPC) bilayers no second protein induced component is observed upon incorporation of M13 coat protein. However, strong effects are detected on the ESR lineshapes upon changing the protein concentration. The ESR lineshapes are simulated by assuming a fixed ratio between the parallel (D) and perpendicular (D) diffusion coefficients of 4, and an order parameter equal to zero. It is found that increasing the protein concentration from L/P to L/P 15 results in a decrease of the rotational diffusion coefficient D from 3.4 × 10⁷ to 1.9 × 10⁷ s^–1. In the time-resolved fluorescence experiments with DPH-propionic acid as a probe, it is observed that increasing the M13 coat protein concentration causes an increase of the two fluorescent lifetimes, indicating an increase in bilayer order. Analysis of the time-resolved fluorescence anisotropy decay allows one to quantitatively determine the order parameters P₂ and P₄, and the rotational diffusion coefficient D of the fluorescent probe. The order parameters P₂ and P₄ increase from 0.34 to 0.55 and from 0.59 to 0.77, respectively, upon adding M13 coat protein to DOPC bilayers with an L/P ratio of 35. The rotational diffusion coefficient D of the DPH-propionic acid probe decreases on incorporating M13 coat protein, in accordance with the ESR results. It is concluded that M13 coat protein in the -monomeric state is not able to produce a long living lipid boundary shell and consequently an immobilization of the lipids. An overall effect on the lipids is induced, resulting in a reduction in the dynamics and an increase in average lipid order. The hydrophobic region of M13 coat protein is proposed to perfectly match the lipid bilayer, resulting in a relatively small distortion of the bilayer structure of the lipid system.     

Depolarized light-scattering studies of bilayer structures in phospholipid vesicles

Depolarized light scattering has been used to investigate the hydrocarbon chain packing of phospholipids in vesicles below the phase transition and ordering of their chains above the phase transition. The chain packing and ordering have been demonstrated for vesicles of l-α-dipalmitoylphosphatidylethanolamine and some phosphatidylcholines of different hydrocarbon chain lenghts. Anisotropy ratios for phospholipid vesicles could be determined by measuring depolarization ratios for several vesicle sizes at low concentrations of the lipids. The following results were obtained. Hydrocarbon chains of l-α-dimyristoyl and distearoylphosphatidylcholines below their phase transitions pack at tilting angles in good agreement with X-ray diffraction data. On the other hand, hydrocarbon chains of dipalmitoylphosphatidylethanolamine pack perpendicular to the bilayer surface. Values of the averaged order parameter for dimyristoyl, dipalmitoyl and distearoylphosphatidylcholines at 2.5°C above their phase transition are all the same and the value for dipalmitoylphosphatidylcholine is in agreement with results from ²H-NMR experiments. The value of the order parameter for dipalmitoylphosphatidylethanolamine is slightly larger than that for dipalmitoylphosphatidylcholine.     

Voice Pathologies Classification and Detection Using EMD-DWT Analysis Based on Higher Order Statistic Features

BackgroundThe voice is a prominent tool allowing people to communicate and to change information in their daily activities. However, any slight alteration in the voice production system may affect the voice quality. Over the last years, researchers in biomedical engineering field worked to develop a robust automatic system that may help clinicians to perform a preventive diagnosis in order to detect the voice pathologies in an early stage.MethodIn this context, pathological voice detection and classification method based on EMD-DWT analysis and Higher Order Statistics (HOS) features, is proposed. Also DWT coefficients features are extracted and tested. To carry out our experiments a wide subset of voice signal from normal subjects and subjects which suffer from the five most frequent pathologies in the Saarbrücken Voice Database (SVD), is selected. In The first step, we applied the Empirical Mode Decomposition (EMD) to the voice signal. Afterwards, among the obtained candidates of Intrinsic Mode Functions (IMFs), we choose the robust one based on temporal energy criterion. In the second step, the selected IMF was decomposed via the Discrete Wavelet Transform (DWT). As a result, two features vector includes six HOSs parameters, and a features vector includes six DWT features were formed from both approximation and detail coefficients. In order to classify the obtained data a support vector machine (SVM) is employed. After having trained the proposed system using the SVD database, the system was evaluated using voice signals of volunteer's subjects from the Neurological department of RABTA Hospital of Tunis.ResultsThe proposed method gives promising results in pathological voices detection. The accuracies reached 99.26% using HOS features and 93.1% using DWT features for SVD database. In the classification, an accuracy of 100% was reached for “Funktionelle Dysphonia vs. Rekrrensparese” based on HOS features. Nevertheless, using DWT features the accuracy achieved was 90.32% for “Hyperfunktionelle Dysphonia vs. Rekurrensparse”. Furthermore, in the validation the accuracies reached were 94.82%, 91.37% for HOS and DWT features, respectively. In the classification the highest accuracies reached were for classifying “Parkinson versus Paralysis” 94.44% and 88.87% based on HOS and DWT features, respectively.ConclusionHOS features show promising results in the automatic voice pathology detection and classification compared to DWT features. Thus, it can reliably be used as noninvasive tool to assist clinical evaluation for pathological voices identification.     

A Molecular Dynamics Investigation of Compressed Aqueous Alkanoate Monolayers

Molecular dynamics are conducted on a dodecanoic acid monolayer/aqueous surface. Surface pressure is controlled by imposing constant-volume conditions for series of lengths of the square slab constituting the MD cell. The response of the alkanoate chains to the pressure is followed by examining various computed quantities that monitor their conformational order. These include atom-pair radial distribution functions, chain torsional angles, energies, atomic densities perpendicular to the interface, diffusivities and atomic plots. These quantities lead to chain separations which in the range 4-5 Å implying order when the alkanoate chains have a mean area of 0.18 nm 2.     

Density functional theory and molecular dynamics investigations on substituted banana-shaped compounds

Density functional theory (DFT) calculations and molecular dynamics (MD) simulations on the atomic level were performed on three different substituted banana-shaped compounds derived from 1,3-phenylene bis[4-(4-n-hexyloxyphenyliminomethyl)benzoate] (P-6-O-PIMB). The DFT studies were carried out on the isolated molecules, and in the MD simulations clusters were treated with up to 64 monomers. The effect of polar substituents, such as chlorine and the nitro group, on the central 1,3-phenylene unit of banana-shaped compounds was investigated. In particular, flexibility, polarity, electrostatic potential (ESP) group charge distributions, B-factors, bending angles and molecular lengths were considered. The MD results were analysed by trajectories of significant torsion angles as well as order parameters such as radial atom pair distribution functions g(r), orientational correlation functions g(o), diffusion coefficients (D) and root mean square deviations (RMSD) values. The g(r) and g(o) values show that a certain long range order is generated by the introduction of a NO₂ group in the 2-position of the central 1,3-phenylene ring. In contrast, the chlorination at the 4 and 6 positions of the central 1,3-phenylene unit decreases the long range order tendency by its perturbation effect on the conformations in such molecules. Moreover, g(r) and g(o) values, as well as diffusion coefficients, show that in the NO₂ substituted compound the formation of microphase areas is preferred. Finally, the aggregation effect in such compounds was studied in a systematic way by a comparison of the conformational properties of the isolated molecules and the monomers in the clusters. Figure Molecular dynamics (MD) simulations on the aggregation behaviour of substituted banana-shaped compounds Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

凝血瀑布机制的序结构分析方法

凝血系统的瀑布机制揭示了凝血因子间的酶促级联反应过程。在级联反应中,各个因子间明显地存在着序关系,而这种序关系的全体构成了系统的序结构。从系统论的观点看,系统的结构是系统性质与功能的基础,因此,通过模型化方法以及利用凝血因子序结构图建立的序结构分析方法,是分析凝血系统各因子相互作用的有用的工具。对蛋白Ｃ及ＴＦＰＩ进行序结构分析,进一步阐明了这两种抑制剂对外源途径凝血的作用特点。     

An investigation of the dynamics of spermine bound to duplex and quadruplex DNA by <Superscript>13</Superscript>C NMR spectroscopy

A detailed analysis of the ¹³C relaxation of ¹³C-labelled spermine bound to duplex and quadruplex DNA is presented. T₁, T₂ and heteronuclear NOE data were collected at four ¹³C frequencies (75.4, 125.7, 150.9 and 201.2 MHz). The data were analyzed in terms of a frequency-dependent order parameter, S ²(ω), to estimate the generalized order parameter and the contributions to the relaxation from different motional frequencies in the picosecond–nanosecond timescale and from any exchange processes that may be occurring on the microsecond–millisecond timescale. The relaxation data was surprisingly similar for spermine bound to two different duplexes and a linear parallel quadruplex. Analysis of the relaxation data from these complexes confirmed the conclusions of previous studies that the dominant motion of spermine is independent of the macroscopic tumbling of the DNA and has an effective correlation time of ∼50 ps. In contrast, spermine bound to a folded antiparallel quadruplex had faster relaxation rates, especially R ₂. As with the other complexes, a fast internal motion of the order of 50 ps makes a substantial contribution to the relaxation. The generalized order parameter for spermine bound to duplex DNA and the linear quadruplex is small but is larger for spermine bound to the folded quadruplex. In the latter case, there is evidence for exchange between at least two populations of spermine occurring on the microsecond–millisecond timescale. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.