Biological and Chemical Physics Commons^™

Novel Materials For Use In Homeland Security Research, Jason Osgood Ewen Young

Masters Theses & Specialist Projects

Organometallic pyridazines and compounds derived from them have been of interest in polymer research due to their atypical environmental stability (as compared to other non-aromatic organic semiconductors) as well as their conductivity. The off-metal synthesis and characterization of several pyridazyl thallium, manganese, and rhenium complexes, beginning with fulvenes 1,2- C5H3(COHR)(COR), are reported here. The diacyl fulvenes were treated with hydrazine hydrate to ring close to pyridazines. Next, the pyridazines were converted to their respective thallium salts through treatment with thallium (I) ethoxide. Lastly, the salts were transmetallated into the respective rhenium or manganese complexes through treatment with the respective metal …

Biophysical Characterization Of Optimized Self-Assembling Protein Nanoparticles As A Malaria Vaccine, Sophia Walker

Honors Scholar Theses

Malaria is an infectious disease that affects several million individuals worldwide and is a significant international public health issue. While there is currently a malaria vaccine in phase III clinical trials, recent results demonstrate that it is only about 35% effective in reducing the incidence of the disease. The use of self-assembling protein nanoparticles (SAPNs) that display epitopes of the repeat sequence of the circumsporozoite protein of Plasmodium falciparum, the parasite that causes malaria, has been shown to elicit a strong immune response. This prototype has potential for further improvement by altering the epitope regions of the nanoparticles to …

In Silico Modeling The Effect Of Single Point Mutations And Rescuing The Effect By Small Molecules Binding, Zhe Zhang

All Dissertations

Single-point mutation in genome, for example, single-nucleotide polymorphism (SNP) or rare genetic mutation, is the change of a single nucleotide for another in the genome sequence. Some of them will result in an amino acid substitution in the corresponding protein sequence (missense mutations); others will not. This investigation focuses on genetic mutations resulting in a change in the amino acid sequence of the corresponding protein. This choice is motivated by the fact that missense mutations are frequently found to affect the native function of proteins by altering their structure, interaction and other properties and cause diseases. A particular disease is …

Enhanced Nucleate Boiling On Horizontal Hydrophobic-Hydrophilic Carbon Nanotube Coatings, Xianming Dai, Xinyu Huang, Fanghao Yang, Xiaodong Li, Joshua Sightler, Yingchao Yang, Chen Li

Faculty Publications

Ideal hydrophobic-hydrophilic composite cavities are highly desired to enhance nucleate boiling. However, it is challenging and costly to fabricate these types of cavities by conventional micro/nano fabrication techniques. In this study, a type of hydrophobic-hydrophilic composite interfaces were synthesized from functionalized multiwall carbon nanotubes by introducing hydrophilic functional groups on the pristine multiwall carbon nanotubes. This type of carbon nanotube enabled hydrophobic-hydrophilic composite interfaces were systematically characterized. Ideal cavities created by the interfaces were experimentally demonstrated to be the primary reason to substantially enhance nucleate boiling

Electric Field-Driven Water Dipoles: Nanoscale Architecture Of Electroporation, Mayya Tokman, Jane Hyojin Lee, Zachary A. Levine, Ming-Chak Ho, Michael E. Colvin, P. Thomas Vernier

Bioelectrics Publications

Electroporation is the formation of permeabilizing structures in the cell membrane under the influence of an externally imposed electric field. The resulting increased permeability of the membrane enables a wide range of biological applications, including the delivery of normally excluded substances into cells. While electroporation is used extensively in biology, biotechnology, and medicine, its molecular mechanism is not well understood. This lack of knowledge limits the ability to control and fine-tune the process. In this article we propose a novel molecular mechanism for the electroporation of a lipid bilayer based on energetics analysis. Using molecular dynamics simulations we demonstrate that …

Ultraviolet Photodissociation Of Ocs: Product Energy And Angular Distributions, George C. Mcbane, Johan A. Schmidt, M. S. Johnson, Reinhard Schinke

Peer Reviewed Articles

The ultraviolet photodissociation of carbonyl sulfide (OCS) was studied using three-dimensional potential energy surfaces and both quantum mechanical dynamics calculations and classical trajectory calculations including surface hopping. The transition dipole moment functions used in an earlier study [J. A. Schmidt, M. S. Johnson, G. C. McBane, and R. Schinke, J. Chem. Phys. 137, 054313 (2012)] were improved with more extensive treatment of excited electronic states. The new functions indicate a much larger contribution from the 1 ¹A" state (¹Σ^- in linear OCS) than was found in the previous work. The new transition dipole functions yield …

Progress In Developing Poisson-Boltzmann Equation Solvers, Chuan Li, Marharyta Petukh, Emil Alexov

Publications

This review outlines the recent progress made in developing more accurate and efficient solutions to model electrostatics in systems comprised of bio-macromolecules and nano-objects, the last one referring to objects that do not have biological function themselves but nowadays are frequently used in biophysical and medical approaches in conjunction with bio-macromolecules. The problem of modeling macromolecular electrostatics is reviewed from two different angles: as a mathematical task provided the specific definition of the system to be modeled and as a physical problem aiming to better capture the phenomena occurring in the real experiments. In addition, specific attention is paid to …

A Rational Free Energy-Based Approach To Understanding And Targeting Disease-Causing Missense Mutations., Zhe Zhang, Shawn Witham, Marharita Petukh, Gautier Moroy, Maria Miteva, Yoshihiko Ikeguchi, Emil Alexov

Publications

BACKGROUND AND SIGNIFICANCE:

Intellectual disability is a condition characterized by significant limitations in cognitive abilities and social/behavioral adaptive skills and is an important reason for pediatric, neurologic, and genetic referrals. Approximately 10% of protein-encoding genes on the X chromosome are implicated in intellectual disability, and the corresponding intellectual disability is termed X-linked ID (XLID). Although few mutations and a small number of families have been identified and XLID is rare, collectively the impact of XLID is significant because patients usually are unable to fully participate in society.

OBJECTIVE:

To reveal the molecular mechanisms of various intellectual disabilities and to suggest …

Enhancing Human Spermine Synthase Activity By Engineered Mutations, Zhe Zhang, Yueli Zheng, Margo Petukh, Anthony Pegg, Yoshihiko Ikeguchi, Emil Alexov

Publications

Spermine synthase (SMS) is an enzyme which function is to convert spermidine into spermine. It was shown that gene defects resulting in amino acid changes of the wild type SMS cause Snyder-Robinson syndrome, which is a mild-to-moderate mental disability associated with osteoporosis, facial asymmetry, thin habitus, hypotonia, and a nonspecific movement disorder. These disease-causing missense mutations were demonstrated, both in silico and in vitro, to affect the wild type function of SMS by either destabilizing the SMS dimer/monomer or directly affecting the hydrogen bond network of the active site of SMS. In contrast to these studies, here we report an …

The Schrödinger Equation With Friction From The Quantum Trajectory Perspective, Sophya V. Garashchuk, Vaibhav Dixit, Bing Gu, James Mazzuca

Faculty Publications

Similarity of equations of motion for the classical and quantum trajectories is used to introduce afriction term dependent on the wavefunction phase into the time-dependent Schrödingerequation. The term describes irreversible energy loss by the quantum system. The force offriction is proportional to the velocity of a quantum trajectory. The resulting Schrödinger equationis nonlinear, conserves wavefunction normalization, and evolves an arbitrary wavefunction into the ground state of the system (of appropriate symmetry if applicable). Decrease in energy is proportional to the average kinetic energy of the quantum trajectory ensemble. Dynamics in the high friction regime is suitable for simple models of …

In Silico Investigation Of Ph-Dependence Of Prolactin And Human Growth Hormone Binding To Human Prolactin Receptor, Lin Wang, Shawn Witham, Zhe Zhang, Michael E. Hodsdon, Emil Alexov

Publications

Experimental data shows that the binding of human prolactin (hPRL) to human prolactin receptor (hPRLr-ECD) is strongly pH-dependent, while the binding of the same receptor to human growth hormone (hGH) is pH-independent. Here we carry in silico analysis of the molecular effects causing such a difference and reveal the role of individual amino acids. It is shown that the computational modeling correctly predicts experimentally determined pKa’s of histidine residues in an unbound state in the majority of the cases and the pH-dependence of the binding free energy. Structural analysis carried in conjunction with calculated pH-dependence of the binding revealed that …

Delphi Web Server: A Comprehensive Online Suite For Electrostatic Calculations Of Biological Macromolecules And Their Complexes., Subhra Sarkar, Shawn Witham, Jie Zhang, Maxim Zhenirovskyy, Walter Rocchia

Publications

Here we report a web server, the DelPhi web server, which utilizes DelPhi program to calculate electrostatic energies and the corresponding electrostatic potential and ionic distributions, and dielectric map. The server provides extra services to fix structural defects, as missing atoms in the structural file and allows for generation of missing hydrogen atoms. The hydrogen placement and the corresponding DelPhi calculations can be done with user selected force field parameters being either Charmm22, Amber98 or OPLS. Upon completion of the calculations, the user is given option to download fixed and protonated structural file, together with the parameter and Delphi output …

Using Delphi Capabilities To Mimic Protein's Conformational Reorganization With Amino Acid Specific Dielectric Constants, Lin Wang, Zhe Zhang, Walter Rocchia, Emil Alexov

Publications

Many molecular events are associated with small or large conformational changes occurring in the corresponding proteins. Modeling such changes is a challenge and requires significant amount of computing time. From point of view of electrostatics, these changes can be viewed as a reorganization of local charges and dipoles in response to the changes of the electrostatic field, if the cause is insertion or deletion of a charged amino acid. Here we report a large scale investigation of modeling the changes of the folding energy due to single mutations involving charged group. This allows the changes of the folding energy to …

Between Algorithm And Model: Different Molecular Surface Definitions For The Poisson-Boltzmann Based Electrostatic Characterization Of Biomolecules In Solution, Sergio Decherchi, José Colmenares, Chiara Eva Catalano, Michela Spagnuolo, Emil Alexov, Walter Rocchia

Publications

The definition of a molecular surface which is physically sound and computationally efficient is a very interesting and long standing problem in the implicit solvent continuum modeling of biomolecular systems as well as in the molecular graphics field. In this work, two molecular surfaces are evaluated with respect to their suitability for electrostatic computation as alternatives to the widely used Connolly-Richards surface: the blobby surface, an implicit Gaussian atom centered surface, and the skin surface. As figures of merit, we considered surface differentiability and surface area continuity with respect to atom positions, and the agreement with explicit solvent simulations. Geometric …

Protein Nano-Object Integrator (Pronoi) For Generating Atomic Style Objects For Molecular Modeling, Nicholas Smith, Brandon Campbell, Lin Li, Chuan Li, Emil Alexov

Publications

Background

With the progress of nanotechnology, one frequently has to model biological macromolecules simultaneously with nano-objects. However, the atomic structures of the nano objects are typically not available or they are solid state entities. Because of that, the researchers have to investigate such nano systems by generating models of the nano objects in a manner that the existing software be able to carry the simulations. In addition, it should allow generating composite objects with complex shape by combining basic geometrical figures and embedding biological macromolecules within the system.

Results

Here we report the Protein Nano-Object Integrator (ProNOI) which allows for …

A Modular Fibrinogen Model That Captures The Stress-Strain Behavior Of Fibrin Fibers, Rodney D. Averett, Bryant Menn, Eric H. Lee, Christine C. Helms, Thomas Barker, Martin Guthold

Physics Faculty Publications

We tested what to our knowledge is a new computational model for fibrin fiber mechanical behavior. The model is composed of three distinct elements: the folded fibrinogen core as seen in the crystal structure, the unstructured α-C connector, and the partially folded α-C domain. Previous studies have highlighted the importance of all three regions and how they may contribute to fibrin fiber stress-strain behavior. Yet no molecular model has been computationally tested that takes into account the individual contributions of all these regions. Constant velocity, steered molecular dynamics studies at 0.025 Å/ps were conducted on the folded fibrinogen …

3d Imaging And Mechanical Modeling Of Helical Buckling In Medicago Truncatula Plant Roots, Jesse L. Silverberg, Roslyn D. Noar, Michael S. Packer, Maria J. Harrison, Christopher L. Henley, Itai Cohen, Sharon J. Gerbode

All HMC Faculty Publications and Research

We study the primary root growth of wild-type Medicago truncatula plants in heterogeneous environments using 3D time-lapse imaging. The growth medium is a transparent hydrogel consisting of a stiff lower layer and a compliant upper layer. We find that the roots deform into a helical shape just above the gel layer interface before penetrating into the lower layer. This geometry is interpreted as a combination of growth-induced mechanical buckling modulated by the growth medium and a simultaneous twisting near the root tip. We study the helical morphology as the modulus of the upper gel layer is varied and demonstrate that …

Characterisation Of The Colour Doppler "Twinkle" Artefact, Deirdre Cassidy, Andrew Fagan, Jacinta Browne

Articles

This investigation involved the development of a range of Colour Doppler Twinkle Artefact phantoms to characterise and quantify the “Twinkle” artefact which is often present when an irregular structure is encountered in the imaged field of view. The artefact occurs in both colour and power Doppler ultrasound imaging and manifests as a false depiction of colour velocity information in stationary soft tissue and therefore can cause significant misdiagnosis of areas of flow within the patient. It has been hypothesised that it is generated due to a strongly reflecting medium composed of individual reflectors and therefore becomes a clinical concern when …

Highly Efficient And Exact Method For Parallelization Of Grid-Based Algorithms And Its Implementation In Delphi, Chuan Li, Lin Li, Jie Zhang, Emil Alexov

Publications

The Gauss–Seidel (GS) method is a standard iterative numerical method widely used to solve a system of equations and, in general, is more efficient comparing to other iterative methods, such as the Jacobi method. However, standard implementation of the GS method restricts its utilization in parallel computing due to its requirement of using updated neighboring values (i.e., in current iteration) as soon as they are available. Here, we report an efficient and exact (not requiring assumptions) method to parallelize iterations and to reduce the computational time as a linear/nearly linear function of the number of processes or computing units. In …

The Ultraviolet Spectrum Of Ocs From First Principles: Electronic Transitions, Vibrational Structure And Temperature Dependence, Johan A. Schmidt, M. S. Johnson, George C. Mcbane, Reinhard Schinke

Peer Reviewed Articles

Global three dimensional potential energy surfaces and transition dipole moment functions are calculated for the lowest singlet and triplet states of carbonyl sulfide at the multireference configuration interaction level of theory. The first ultraviolet absorption band is then studied by means of quantum mechanical wave packet propagation. excitation of the repulsive 2¹A' state gives the main contribution to the cross section. Excitation of the repulsive 1¹A" state is about a factor of 20 weaker at the absorption peak (E_ph ≈ 45 000 cm^-1) but becomes comparable to the 2¹A' state …

How The Cucumber Tendril Coils And Overwinds, Sharon J. Gerbode, Joshua R. Puzey, Andrew G. Mccormick, L. Mahadevan

All HMC Faculty Publications and Research

The helical coiling of plant tendrils has fascinated scientists for centuries, yet the underlying mechanism remains elusive. Moreover, despite Darwin’s widely accepted interpretation of coiled tendrils as soft springs, their mechanical behavior remains unknown. Our experiments on cucumber tendrils demonstrate that tendril coiling occurs via asymmetric contraction of an internal fiber ribbon of specialized cells. Under tension, both extracted fiber ribbons and old tendrils exhibit twistless overwinding rather than unwinding, with an initially soft response followed by strong strain-stiffening at large extensions. We explain this behavior using physical models of prestrained rubber strips, geometric arguments, and mathematical models of elastic …

Comparative Review Of Imaging Methods Used For Diagnosing Renal Artery Stenosis (Ras), Deirdre King, Carmel Moran, Jacinta Browne

Articles

This comparative review examines the efficacy of different imaging methods to detect and quantify renal artery stenosis (RAS). Detection of RAS is important because it can lead to renovascular hypertension which is the most common form of secondary hypertension. Furthermore, it is important that a RAS is detected as early as possible as it is a potentially correctable cause of hypertension.¹ If detected at an early stage RAS can potentially be treated using a minimally invasive drug treatment regimen rather than the more invasive percutaneous transluminal renal angioplasty without or with stent placement or surgery. Currently there are a …

Angular And Dynamical Properties In Resonant Inelastic X-Ray Scattering: Case Study Of Chlorine-Containing Molecules, Renaud Guillemin, Wayne C. Stolte, Loic Journel, Stephane Carniato, Maria Novella Piancastelli, Dennis W. Lindle, Marc Simon

Chemistry and Biochemistry Faculty Research

Polarization-dependent resonant inelastic x-ray scattering (RIXS) has been shown to be a probe of molecular-field effects on the electronic structure of isolated molecules. In this experimental analysis we explain the linear dichroism observed in Cl 2p polarized RIXS following Cl 1s excitation of a series of chlorofluoromethanes (CF3Cl, CF2Cl2, CFCl3, and CCl4) as due to molecular-field effects, including singlet-triplet exchange. We present an approach to extract directly the 2p inner-shell electronic state populations from the experimental measurements. Using the angular properties of the measured KV emission we also are able to determine the value of the polarization anisotropy parameter βp …

Predicting Nonspecific Ion Binding Using Delphi, Marharyta Petukh, Maxim Zhenirovskyy, Chuan Li, Lin Li, Lin Wang, Emil Alexov

Publications

Ions are an important component of the cell and affect the corresponding biological macromolecules either via direct binding or as a screening ion cloud. Although some ion binding is highly specific and frequently associated with the function of the macromolecule, other ions bind to the protein surface nonspecifically, presumably because the electrostatic attraction is strong enough to immobilize them. Here, we test such a scenario and demonstrate that experimentally identified surface-bound ions are located at a potential that facilitates binding, which indicates that the major driving force is the electrostatics. Without taking into consideration geometrical factors and structural fluctuations, we …

Magnetic Ordering And Structural Phase Transition In Strained Ultrathin Srruo3/Srtio3 Superlattice, Mingquiang Gu, Xiaoshan Wu, Guoping Zhang

Symposium 2012

No abstract provided.

Cloning And Characterization Of Sas0754, A Hypothetical Protein From Community Associated Staphylococcus Aureus, Unknown Unknown

Symposium 2012

Community associated Staphylococcus aureus (strain MSSA476) is a gram positive cocci capable of infecting many different parts of the body and known to cause serious infections that can be fatal, such as bacterial arthritis and acute endocarditis. To find effective ways of fighting against CA-MRSA strains we must learn more about their ability to infect. The focus of this study was cloning and characterization of a protein referred to as SAS0754. The size of SAS0754 is 340 amino acids and the gene sequence is 1023 nucleotides. The hypothetical function of this protein is that it is an extracellular matrix binding …

A Convenient Synthesis Of 2,6-Dichlorohomonicotinic Acid, Chase Buchanan, Richard W. Fitch

Symposium 2012

In our synthetic efforts toward the alkaloid phantasmidine, we required a convenient source of the title compound. Herein, we describe a short synthesis of 2,6-dichlorohomonicotinic acid by direct allylation of 2,6-dichloropyridine with LDA/allyl chloride, followed by permanganate oxidation of the side chain [figure1]. Yields for the allylation are high, while permanganate oxidation required more adjustment. Successful conditions require the modest acidification of the mixture with acetic acid and cleanup by acid base workup. No chromatography is needed.

Convenient Parallel Synthesis Of Alkyl- And Aryl-S-Tert-Butyl Thiothers, Rebecca Norcross, Jessica Stanfield, Richard W. Fitch

Symposium 2012

While preparing novel cysteine derivatives as oxidation catalysts, we needed S-tert-butylcysteine. We also examined acid-promoted tert-butylation of thiols using tert-butanol as reagent and solvent. While cysteine and aminoethanethiol work well using tBuOH in 4M HCl, other thiols fail in the aqueous environment and aerobic conditions. We examined a variety of aliphatic and aromatic thiols in tBuOH with H2SO4 catalysis and found that argon sparging and the use of 1 eq of acid led to good yields in a parallel format.

Use Of Second Harmonic Generation (Shg) Imaging For 3-Dimensional Ultrastructural Visualization Of Muscle Repair Mechanisms, Matthew Dufner

Honors Scholar Theses

In this study, we have combined SHG imaging with various fluorescent dyes which are designed to stain nuclei and used a skeletal muscle injury and regeneration model to establish the ability of this approach to reliably and reproducibly evaluate the above nuclear parameters. By using the cobra cardiotoxin (CTX-1), which creates acute well defined injuries within the muscle, on the tibialis anterior (TA) and gastrocnemius hind limb muscles of mice, predictable and reproducible regenerative patterns (in response to acute injury) can be observed by harvesting muscle samples at specific time points during recovery. Through SHG imaging, we endeavor to document …

Delphi: A Comprehensive Suite For Delphi Software And Associated Resources, Lin Li, Chuan Li, Subhra Sarkar, Jie Zhang, Shawn Witham, Zhe Zhang, Lin Wang, Nicholas Smith, Marharyta Petukh, Emil Alexov

Publications

Background

Accurate modeling of electrostatic potential and corresponding energies becomes increasingly important for understanding properties of biological macromolecules and their complexes. However, this is not an easy task due to the irregular shape of biological entities and the presence of water and mobile ions.

Results

Here we report a comprehensive suite for the well-known Poisson-Boltzmann solver, DelPhi, enriched with additional features to facilitate DelPhi usage. The suite allows for easy download of both DelPhi executable files and source code along with a makefile for local installations. The users can obtain the DelPhi manual and parameter files required for the corresponding …