Eigenvector Centrality Distribution for Characterization of Protein Allosteric Pathways

Determining the principal energy pathways for allosteric communication in biomolecules, that occur as a result of thermal motion, remains challenging due to the intrinsic complexity of the systems involved. Graph theory provides an approach for making sense of such complexity, where allosteric proteins can be represented as networks of amino acids. In this work, we establish the eigenvector centrality metric in terms of the mutual information, as a mean of elucidating the allosteric mechanism that regulates the enzymatic activity of proteins. Moreover, we propose a strategy to characterize the range of the physical interactions that underlie the allosteric process. In particular, the well known enzyme, imidazol glycerol phosphate synthase (IGPS), is utilized to test the proposed methodology. The eigenvector centrality measurement successfully describes the allosteric pathways of IGPS, and allows to pinpoint key amino acids in terms of their relevance in the momentum transfer process. The resulting insight can be utilized for refining the control of IGPS activity, widening the scope for its engineering. Furthermore, we propose a new centrality metric quantifying the relevance of the surroundings of each residue. In addition, the proposed technique is validated against experimental solution NMR measurements yielding fully consistent results. Overall, the methodologies proposed in the present work constitute a powerful and cost effective strategy to gain insight on the allosteric mechanism of proteins

Distributed Control of Microscopic Robots in Biomedical Applications

Current developments in molecular electronics, motors and chemical sensors could enable constructing large numbers of devices able to sense, compute and act in micron-scale environments. Such microscopic machines, of sizes comparable to bacteria, could simultaneously monitor entire populations of cells individually in vivo. This paper reviews plausible capabilities for microscopic robots and the physical constraints due to operation in fluids at low Reynolds number, diffusion-limited sensing and thermal noise from Brownian motion. Simple distributed controls are then presented in the context of prototypical biomedical tasks, which require control decisions on millisecond time scales. The resulting behaviors illustrate trade-offs among speed, accuracy and resource use. A specific example is monitoring for patterns of chemicals in a flowing fluid released at chemically distinctive sites. Information collected from a large number of such devices allows estimating properties of cell-sized chemical sources in a macroscopic volume. The microscopic devices moving with the fluid flow in small blood vessels can detect chemicals released by tissues in response to localized injury or infection. We find the devices can readily discriminate a single cell-sized chemical source from the background chemical concentration, providing high-resolution sensing in both time and space. By contrast, such a source would be difficult to distinguish from background when diluted throughout the blood volume as obtained with a blood sample

A Novel A Priori Simulation Algorithm for Absorbing Receivers in Diffusion-Based Molecular Communication Systems

A novel a priori Monte Carlo (APMC) algorithm is proposed to accurately simulate the molecules absorbed at spherical receiver(s) with low computational complexity in diffusion-based molecular communication (MC) systems. It is demonstrated that the APMC algorithm achieves high simulation efficiency since by using this algorithm, the fraction of molecules absorbed for a relatively large time step length precisely matches the analytical result. Therefore, the APMC algorithm overcomes the shortcoming of the existing refined Monte Carlo (RMC) algorithm which enables accurate simulation for a relatively small time step length only. Moreover, for the RMC algorithm, an expression is proposed to quickly predict the simulation accuracy as a function of the time step length and system parameters, which facilitates the choice of simulation time step for a given system. Furthermore, a rejection threshold is proposed for both the RMC and APMC algorithms to significantly save computational complexity while causing an extremely small loss in accuracy.Comment: 11 pages, 14 figures, submitted to IEEE Transactions on NanoBioscience. arXiv admin note: text overlap with arXiv:1803.0463

Field-induced charge transport at the surface of pentacene single crystals: a method to study charge dynamics of 2D electron systems in organic crystals

A method has been developed to inject mobile charges at the surface of organic molecular crystals, and the DC transport of field-induced holes has been measured at the surface of pentacene single crystals. To minimize damage to the soft and fragile surface, the crystals are attached to a pre-fabricated substrate which incorporates a gate dielectric (SiO_2) and four probe pads. The surface mobility of the pentacene crystals ranges from 0.1 to 0.5 cm^2/Vs and is nearly temperature-independent above ~150 K, while it becomes thermally activated at lower temperatures when the induced charges become localized. Ruling out the influence of electric contacts and crystal grain boundaries, the results contribute to the microscopic understanding of trapping and detrapping mechanisms in organic molecular crystals.Comment: 14 pages, 4 figures. Submitted to J. Appl. Phy