We introduce a new class of methods, denoted as Truncated Conjugate Gradient(TCG), to solve the many-body polarization energy and its associated forces in molecular simulations (i.e. molecular dynamics (MD) and Monte Carlo). The method consists in a fixed number of Conjugate Gradient (CG) iterations. TCG approaches provide a scalable solution to the polarization problem at a user-chosen cost and a corresponding optimal accuracy. The optimality of the CG-method guarantees that the number of the required matrix-vector products are reduced to a minimum compared to other iterative methods. This family of methods is non-empirical, fully adaptive, and provides analytical gradients, avoiding therefore any energy drift in MD as compared to popular iterative solvers. Besides speed, one great advantage of this class of approximate methods is that their accuracy is systematically improvable. Indeed, as the CG-method is a Krylov subspace method, the associated error is monotonically reduced at each iteration. On top of that, two improvements can be proposed at virtually no cost: (i) the use of preconditioners can be employed, which leads to the Truncated Preconditioned Conjugate Gradient (TPCG); (ii) since the residual of the final step of the CG-method is available, one additional Picard fixed point iteration ("peek"), equivalent to one step of Jacobi Over Relaxation (JOR) with relaxation parameter omega, can be made at almost no cost. This method is denoted by TCG-n(omega). Black-box adaptive methods to find good choices of omega are provided and discussed. Results show that TPCG-3(omega) is converged to high accuracy (a few kcal/mol) for various types of systems including proteins and highly charged systems at the fixed cost of four matrix-vector products: three CG iterations plus the initial CG descent direction. Alternatively, T(P)CG-2(omega) provides robust results at a reduced cost (three matrix-vector products) and offers new perspectives for long polarizable MD as a production algorithm. The T(P)CG-1(omega) level provides less accurate solutions for inhomogeneous systems, but its applicability to well-conditioned problems such as water is remarkable, with only two matrix-vector product evaluations.
Implanted brain electrodes construct the only means to electrically interface with individual neurons in vivo, but their recording efficacy and biocompatibility pose limitations on scientific and clinical applications. We showed that nanoelectronic thread (NET) electrodes with subcellular dimensions, ultraflexibility, and cellular surgical footprints form reliable, glial scar–free neural integration. We demonstrated that NET electrodes reliably detected and tracked individual units for months; their impedance, noise level, single-unit recording yield, and the signal amplitude remained stable during long-term implantation. In vivo two-photon imaging and postmortem histological analysis revealed seamless, subcellular integration of NET probes with the local cellular and vasculature networks, featuring fully recovered capillaries with an intact blood-brain barrier and complete absence of chronic neuronal degradation and glial scar.
A nonintrusive measure of the exhaust plume and immediate sound field produced by a cluster of two thrust optimized parabolic contour nozzles is studied during two steady-state conditions. The first condition is at a nozzle pressure ratio of 25, at which point the flow is in a restricted-shock separated state. The second condition is at a nozzle pressure ratio of 37 and is when the flow and internal shock pattern transition rapidly between free-shock separated flow and the end-effects regime. These end-effects regime pulsations produce significant vibroacoustic loads due to the intermittent breathing of the last trapped annular separation bubble with the ambient. The exhaust plumes and surrounding sound field are first visualized by way of retroreflective shadowgraphy. Radon transforms of the spatially resolved shadowgraphy images are then used to characterize the statistical behavior of the acoustic wave fronts that reside within the hydrodynamic periphery of the nozzle flow. The findings reveal quantitative evidence of the sources of most intense vibroacoustic loads during the end-effects regime of clustered rockets.
Molecular recognition is of paramount interest in many applications. Here we investigate a series of host-guest systems previously used in the SAMPL4 blind challenge by using molecular simulations and the AMOEBA polarizable force field. The free energy results computed by Bennett's acceptance ratio (BAR) method using the AMOEBA polarizable force field ranked favorably among the entries submitted to the SAMPL4 host-guest competition [Muddana, et al., J. Comput.-Aided Mol. Des., 2014, 28, 305-317]. In this work we conduct an in-depth analysis of the AMOEBA force field host-guest binding thermodynamics by using both BAR and the orthogonal space random walk (OSRW) methods. The binding entropy-enthalpy contributions are analyzed for each host-guest system. For systems of inordinate binding entropy-enthalpy values, we further examine the hydrogen bonding patterns and configurational entropy contribution. The binding mechanism of this series of host-guest systems varies from ligand to ligand, driven by enthalpy and/or entropy changes. Convergence of BAR and OSRW binding free energy methods is discussed. Ultimately, this work illustrates the value of molecular modelling and advanced force fields for the exploration and interpretation of binding thermodynamics.
Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) methods have become widely adopted in estimating protein-ligand binding affinities due to their efficiency and high correlation with experiment. Here different computational alternatives were investigated to assess their impact to the agreement of MMPBSA calculations with experiment. Seven receptor families with both high-quality crystal structures and binding affinities were selected. First the performance of nonpolar solvation models was studied and it was found that the modern approach that separately models hydrophobic and dispersion interactions dramatically reduces RMSD's of computed relative binding affinities. The numerical setup of the Poisson-Boltzmann methods was analyzed next. The data shows that the impact of grid spacing to the quality of MMPBSA calculations is small: the numerical error at the grid spacing of 0.5 A is already small enough to be negligible. The impact of different atomic radius sets and different molecular surface definitions was further analyzed and weak influences were found on the agreement with experiment. The influence of solute dielectric constant was also analyzed: a higher dielectric constant generally improves the overall agreement with experiment, especially for highly charged binding pockets. The data also showed that the converged simulations caused slight reduction in the agreement with experiment. Finally the direction of estimating absolute binding free energies was briefly explored. Upon correction of the binding-induced rearrangement free energy and the binding entropy lost, the errors in absolute binding affinities were also reduced dramatically when the modern nonpolar solvent model was used, although further developments were apparently necessary to further improve the MMPBSA methods. (c) 2016 Wiley Periodicals, Inc.
The spatial evolution of acoustic waveforms produced by a laboratory-scale Mach 3 jet are investigated using both 1∕4 in. and 1∕8 in. pressure field microphones located along rays emanating from the postpotential core where the peak sound emission is found to occur. The measurements are acquired in a fully anechoic chamber, where ground or other large surface reflections are minimal. Various statistical metrics are examined along the peak emission path, where they are shown to undergo rapid changes within 2m from the source region. An experimentally validated wave-packet model is then used to confirm the location where the pressure amplitude along the peak emission path transitions from cylindrical to spherical decay. Various source amplitudes, provided by the wave-packet model, are then used to estimate shock formation distance and Gol’dberg numbers for diverging waves. The findings suggest that cumulative nonlinear distortion is likely to occur at laboratory scale near the jet flow, where the waveform amplitude decays cylindrically, but less likely to occur farther from the jet flow, where the waveform amplitude decays spherically. Direct inspection of the raw time series reveals how steepened waveforms are generated by rogue like waves that form from the constructive interference of waves from neighboring sources as opposed to classical cumulative nonlinear distortion.
Abstract. We illustrate wide-field imaging of skin using a structured light (SL) approach that highlights the contrast from superficial tissue scattering. Setting the spatial frequency of the SL in a regime that limits the penetration depth effectively gates the image for photons that originate from the skin surface. Further, rendering the SL images in a color format provides an intuitive format for viewing skin pathologies. We demonstrate this approach in skin pathologies using a custom-built handheld SL imaging system.