Physics Commons^™

Progress In The Prediction Of Pka Values In Proteins, Emil Alexov, Ernest L. Mehler, Nathan Baker, Antonio Baptista, Yong Huang, Francesca Milletti, Jens Erik Nielsen, Damien Farrell, Tommy Carstensen, Mats H.M. Olsson, Jana K. Shen, Jim Warwicker, Sarah Williams, J Michael Word

Publications

The pK_a-cooperative aims to provide a forum for experimental and theoretical researchers interested in protein pK_a values and protein electrostatics in general. The first round of the pK_a-cooperative, which challenged computational labs to carry out blind predictions against pK_as experimentally determined in the laboratory of Bertrand Garcia-Moreno, was completed and results discussed at the Telluride meeting (July 6–10, 2009). This article serves as an introduction to the reports submitted by the blind prediction participants that will be published in a special issue of PROTEINS: Structure, Function and Bioinformatics. …

Developing Hybrid Approaches To Predict Pka Values Of Ionizable Groups, Shawn Witham, Kemper Talley, Lin Wang, Zhe Zhang, Daquan Gao, Wei Yang, Emil Alexov

Publications

Accurate predictions of pKa values of titratable groups require taking into account all relevant processes associated with the ionization/deionization. Frequently, however, the ionization does not involve significant structural changes and the dominating effects are purely electrostatic in origin allowing accurate predictions to be made based on the electrostatic energy difference between ionized and neutral forms alone using a static structure. On another hand, if the change of the charge state is accompanied by a structural reorganization of the target protein, then the relevant conformational changes have to be taken into account in the pKa calculations. Here we report a hybrid …

Understanding The Molecular Information Contained In Principal Component Analysis Of Vibrational Spectra Of Biological Systems, Franck Bonnier, Hugh Byrne

Articles

K-means clustering followed by Principal Component Analysis (PCA) is employed to analyse Raman spectroscopic maps of single biological cells. K-means clustering successfully identifies regions of cellular cytoplasm, nucleus and nucleoli, but the mean spectra do not differentiate their biochemical composition. The loadings of the principal components identified by PCA shed further light on the spectral basis for differentiation but they are complex and, as the number of spectra per cluster is imbalanced, particularly in the case of the nucleoli, the loadings under-represent the basis for differentiation of some cellular regions. Analysis of pure bio-molecules, both structurally and spectrally distinct, in …

Evolution Of Spur-Length Diversity In Aquilegia Petals Is Achieved Solely Through Cell-Shape Anisotropy, Joshua R. Puzey, Sharon J. Gerbode, Scott A. Hodges, Elena M. Kramer, L. Mahadevan

All HMC Faculty Publications and Research

The role of petal spurs and specialized pollinator interactions has been studied since Darwin. Aquilegia petal spurs exhibit striking size and shape diversity, correlated with specialized pollinators ranging from bees to hawkmoths in a textbook example of adaptive radiation. Despite the evolutionary significance of spur length, remarkably little is known about Aquilegia spur morphogenesis and its evolution. Using experimental measurements, both at tissue and cellular levels, combined with numerical modelling, we have investigated the relative roles of cell divisions and cell shape in determining the morphology of the Aquilegia petal spur. Contrary to decades-old hypotheses implicating a discrete meristematic zone …

Toward High-Performance Nanostructured Thermoelectric Materials: The Progress Of Bottom-Up Solution Chemistry Approaches, Yixin Zhao, Jeffrey S. Dyck, Clemens Burda

Physics

Significant research effort has recently gone into the synthesis of thermoelectric nanomaterials through different chemical approaches since nanomaterials chemistry became a promising strategy for improving thermoelectric performance. Different thermoelectric nanocrystals, especially PbTe, Bi₂Te₃ and CoSb₃, with various compositions and morphologies have been successfully prepared by solvo/hydrothermal, electrochemical, and ligand-based synthesis methods. Such nanoscale materials show not only substantial reduction in thermal conductivity due to increased phonon scattering at nanoscale grain boundaries and lower densities of phonon states but possibly also an enhancement in thermopower due to electronic quantum size effects. More recently, the notoriously low …

Region-Of-Interest Material Decomposition From Truncated Energy-Resolved Ct, Taly Gilat Schmidt

Biomedical Engineering Faculty Research and Publications

Purpose: Energy-resolved CT using photon-counting detectors has the potential to provide improved material decomposition compared to dual-kVp approaches. However, available photon-counting detectors are susceptible to pulse-pileup artifacts, especially at the periphery of the field of view (FOV) where the object attenuation is low compared to the center of the FOV. Pulse pileup may be avoided by imaging a region-of-interest (ROI) where the dynamic range is expected to be limited. This work investigated performing material decomposition and reconstructing ROI basis images from truncated energy-resolved data.

Methods: A method is proposed to reconstructimages of basis functions primarily contained within the ROI, such …

A Missense Mutation In Clic2 Associated With Intellectual Disability Is Predicted By In Silico Modeling To Affect Protein Stability And Dynamics, Shawn Witham, Kyoko Takano, Charles Schwartz, Emil Alexov

Publications

Large-scale next generation resequencing of X chromosome genes identified a missense mutation in the CLIC2 gene on Xq28 in a male with X-linked intellectual disability (XLID) and not found in healthy individuals. At the same time, numerous nsSNPs (nonsynonomous SNP) have been reported in the CLIC2 gene in healthy individuals indicating that the CLIC2 protein can tolerate amino acid substitutions and be fully functional. To test the possibility that p.H101Q is a disease-causing mutation, we performed in silico simulations to calculate the effects of the p.H101Q mutation on CLIC2 stability, dynamics, and ionization states while comparing the effects obtained for …

Relativistic Transformation Of Phase-Space Distributions, R A. Treumann, R Nakamura, W Baumjohann

Dartmouth Scholarship

We investigate the transformation of the distri- bution function in the relativistic case, a problem of interest in plasma when particles with high (relativistic) velocities come into play as for instance in radiation belt physics, in the electron-cyclotron maser radiation theory, in the vicin- ity of high-Mach number shocks where particles are acceler- ated to high speeds, and generally in solar and astrophysical plasmas. We show that the phase-space volume element is a Lorentz constant and construct the general particle distri- bution function from first principles. Application to thermal equilibrium lets us derive a modified version of the isotropic relativisticthermaldistribution,themodifiedJu …

Photodissociation Of N2O: Energy Partitioning, Johan A. Schmidt, M. S. Johnson, U. Lorenz, George C. Mcbane, Reinhard Schinke

Peer Reviewed Articles

The energy partitioning in the UV photodissociation of N₂O is investigated by means of quantum mechanical wave packet and classical trajectory calculations using recently calculated potential energy surfaces. Vibrational excitation of N₂ is weak at the onset of the absorption spectrum, but becomes stronger with increasing photon energy. Since the NNO equilibrium angles in the ground and the excited state differe by about 70°, the molecule experiences an extraordinarily large torque during fragmentation producing N₂in very high rotational states. The vibrational and rotational distributions obtained from the quantum mechanical and the classical calculations agree remarkably …

On The Role Of Electrostatics In Protein–Protein Interactions, Zhe Zhang, Shawn Witham, Emil Alexov

Publications

The role of electrostatics in protein–protein interactions and binding is reviewed in this paper. A brief outline of the computational modeling, in the framework of continuum electrostatics, is presented and the basic electrostatic effects occurring upon the formation of the complex are discussed. The effect of the salt concentration and pH of the water phase on protein–protein binding free energy is demonstrated which indicates that the increase of the salt concentration tends to weaken the binding, an observation that is attributed to the optimization of the charge–charge interactions across the interface. It is pointed out that the pH-optimum (pH of …

Communication: Bubbles, Crystals, And Laser-Induced Nucleation, Brandon C. Knott, Jerry L. Larue, Alec M. Wodtke, Michael F. Doherty, Baron Peters

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Short intense laser pulses of visible and infrared light can dramatically accelerate crystal nucleation from transparent solutions; previous studies invoke mechanisms that are only applicable for nucleation of ordered phases or high dielectric phases. However, we show that similar laser pulses induce CO₂bubblenucleation in carbonated water. Additionally, in water that is cosupersaturated with argon and glycine, argon bubbles escaping from the water can induce crystal nucleation without a laser. Our findings suggest a possible link between laser-induced nucleation of bubbles and crystals.

In Silico And In Vitro Investigations Of The Mutability Of Disease-Causing Missense Mutation Sites In Spermine Synthase, Zhe Zhang, Joy Norris, Charles Schwartz, Emil Alexov

Publications

Background

Spermine synthase (SMS) is a key enzyme controlling the concentration of spermidine and spermine in the cell. The importance of SMS is manifested by the fact that single missense mutations were found to cause Snyder-Robinson Syndrome (SRS). At the same time, currently there are no non-synonymous single nucleoside polymorphisms, nsSNPs (harmless mutations), found in SMS, which may imply that the SMS does not tolerate amino acid substitutions, i.e. is not mutable.

Methodology/Principal Findings

To investigate the mutability of the SMS, we carried out in silico analysis and in vitro experiments of the effects of amino acid substitutions at the …

The Economics Of The Atomic Bomb: Cost And Utilization, Jonathan M. Davis Mr.

Senior Honors Theses

Few moments in human history can be compared to the culmination of events that brought the atomic bomb into creation. It is incredible to contemplate that while a nation was fighting a two front war that spanned from Europe into the Pacific, that the United States was able to utilize the time, energy, brains, materials, manpower, and capital to complete a project in four years. That under any other circumstances would have taken greater than half a century to complete.

First, this thesis will discuss breakthroughs in research that led scientists to believe that the atomic weapons could be built, …

Macular Pigment: Practical Implications For Optometric Practice In Preventative Health Care And Visual Performance Enhancement, Grainne Scanlon

Masters

The macula is a specialised part of the retina responsible for detailed central and colour vision. The carotenoids, lutein, zeaxanthin and meso-zeaxanthin are uniquely concentrated in the inner and central layers of the primate macula, where they are known as macular pigment (MP). It has been shown that MP is entirely of dietary origin and that lutein and zeaxanthin levels in serum, diet and retina correlate. Age-Related Macular Degeneration (AMD) is a disease of the macula and results in loss of central vision. MP, because of its optical filtration and antioxidant properties, may have an important role in the prevention …

Collisional Transfer Of Population And Orientation In Nak, Seth T. Ashman, C. M. Wolfe, J. Bai, B. Beser, E. H. Ahmed, A. M. Lyyra, J. Huennekens

Engineering & Physics Faculty Publications

Collisional satellite lines with |ΔJ| ≤ 58 have been identified in recent polarization spectroscopy V-type optical–optical double resonance (OODR) excitation spectra of the Rb₂ molecule [H. Salami et al., Phys. Rev.A80, 022515 (2009)]. Observation of these satellite lines clearly requires a transfer of population from the rotational level directly excited by the pump laser to a neighboring level in a collision of the molecule with an atomic perturber. However to be observed in polarization spectroscopy, the collision must also partially preserve the angular momentum orientation, which is at least somewhat surprising given the extremely large values of …

Wave-Function Functionals For The Density, Marlina Slamet

Physics Faculty Publications

We extend the idea of the constrained-search variational method for the construction of wave-function functionals ψ[χ] of functions χ. The search is constrained to those functions χ such that ψ[χ] reproduces the density ρ(r) while simultaneously leading to an upper bound to the energy. The functionals are thereby normalized and automatically satisfy the electron-nucleus coalescence condition. The functionals ψ[χ] are also constructed to satisfy the electron-electron coalescence condition. The method is applied to the ground state of the helium atom to construct functionals ψ[χ] that reproduce the density as given by the Kinoshita correlated wave function. The expectation …

Ultrafast Rempi In Benzene And The Monohalobenzenes Without The Focal Volume Effect, Timothy D. Scarborough, James Strohaber, David B. Foote, Collin J. Mcacy, Cornelis J. Uiterwaal

C.J.G.J. Uiterwaal Publications

We report on the photoionization and photofragmentation of benzene (C₆H₆) and of the monohalobenzenes C₆H₅–X (X = F, Cl, Br, I) under intense-field, single-molecule conditions. We focus 50-fs, 804-nm pulses from a Ti:sapphire laser source, and record ion mass spectra as a function of intensity in the range ~10¹³ W/cm² to ~10¹⁵ W/cm². We count ions that were created in the central, most intense part of the focal area; ions from other regions are rejected. For all targets, stable parent ions (C₆H₅X+) are …

Comparative Imaging Study In Ultrasound, Mri, Ct And Dsa Using A Multi-Modality Renal Artery Phantom, Deirdre King, Andrew Fagan, Carmel Moran, Jacinta Browne

Articles

A range of anatomically realistic multimodality renal artery phantoms consisting of vessels with varying degrees of stenosis was developed and evaluated using four imaging techniques currently used to detect renal artery stenosis (RAS). The spatial resolution required to visualize vascular geometry and the velocity detection performance required to adequately characterize blood flow in patients suffering from RAS are currently ill-defined, with the result that no one imaging modality has emerged as a gold standard technique for screening for this disease.

Methods:

The phantoms, which contained a range of stenosis values (0%, 30%, 50%, 70%, and 85%), were designed for use …