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Description
The continuous random network (CRN) model of network glasses is widely accepted as a model for materials such as vitreous silica and amorphous silicon. Although it

has been more than eighty years since the proposal of the CRN, there has not been conclusive experimental evidence of the structure of glasses and

The continuous random network (CRN) model of network glasses is widely accepted as a model for materials such as vitreous silica and amorphous silicon. Although it

has been more than eighty years since the proposal of the CRN, there has not been conclusive experimental evidence of the structure of glasses and amorphous

materials. This has now changed with the advent of two-dimensional amorphous materials. Now, not only the distribution of rings but the actual atomic ring

structure can be imaged in real space, allowing for greater charicterization of these types of networks. This dissertation reports the first work done

on the modelling of amorphous graphene and vitreous silica bilayers. Models of amorphous graphene have been created using a Monte Carlo bond-switching method

and MD method. Vitreous silica bilayers have been constructed using models of amorphous graphene and the ring statistics of silica bilayers has been studied.
ContributorsKumar, Avishek (Author) / Thorpe, Michael F (Thesis advisor) / Ozkan, Sefika B (Committee member) / Beckstein, Oliver (Committee member) / Treacy, Michael Mj (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Molecular dynamics simulations were used to study properties of water at the interface with nanometer-size solutes. We simulated nonpolar attractive Kihara cavities given by a Lennard-Jones potential shifted by a core radius. The dipolar response of the hydration layer to a uniform electric field substantially exceeds that of the bulk.

Molecular dynamics simulations were used to study properties of water at the interface with nanometer-size solutes. We simulated nonpolar attractive Kihara cavities given by a Lennard-Jones potential shifted by a core radius. The dipolar response of the hydration layer to a uniform electric field substantially exceeds that of the bulk. For strongly attractive solutes, the collective dynamics of the hydration layer become slow compared to bulk water, as the solute size is increased. The statistics of electric field fluctuations at the solute center are Gaussian and tend toward the dielectric continuum limit with increasing solute size. A dipolar probe placed at the center of the solute is sensitive neither to the polarity excess nor to the slowed dynamics of the hydration layer. A point dipole was introduced close to the solute-water interface to further study the statistics of electric field fluctuations generated by the water. For small dipole magnitudes, the free energy surface is single-welled, with approximately Gaussian statistics. When the dipole is increased, the free energy surface becomes double-welled, before landing in an excited state, characterized again by a single-welled surface. The intermediate region is fairly broad and is characterized by electrostatic fluctuations significantly in excess of the prediction of linear response. We simulated a solute having the geometry of C180 fullerene, with dipoles introduced on each carbon. For small dipole moments, the solvent response follows the results seen for a single dipole; but for larger dipole magnitudes, the fluctuations of the solute-solvent energy pass through a second maximum. The juxtaposition of the two transitions leads to an approximately cubic scaling of the chemical potential with the dipole strengh. Umbrella sampling techniques were used to generate free energy surfaces of the electric potential fluctuations at the heme iron in Cytochrome B562. The results were unfortunately inconclusive, as the ionic background was not effectively represented in the finite-size system.
ContributorsFriesen, Allan Dwayne (Author) / Matyushov, Dmitry V (Thesis advisor) / Angell, C Austen (Thesis advisor) / Beckstein, Oliver (Committee member) / Mujica, Vladimiro (Committee member) / Arizona State University (Publisher)
Created2012
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Description
The goal of this theoretical study of infrared spectra was to ascertain to what degree molecules may be identified from their IR spectra and which spectral regions are best suited for this purpose. The frequencies considered range from the lowest frequency molecular vibrations in the far-IR, terahertz region (below ~3

The goal of this theoretical study of infrared spectra was to ascertain to what degree molecules may be identified from their IR spectra and which spectral regions are best suited for this purpose. The frequencies considered range from the lowest frequency molecular vibrations in the far-IR, terahertz region (below ~3 THz or 100 cm-1) up to the highest frequency vibrations (~120 THz or 4000 cm-1). An emphasis was placed on the IR spectra of chemical and biological threat molecules in the interest of detection and prevention. To calculate IR spectra, the technique of normal mode analysis was applied to organic molecules ranging in size from 8 to 11,352 atoms. The IR intensities of the vibrational modes were calculated in terms of the derivative of the molecular dipole moment with respect to each normal coordinate. Three sets of molecules were studied: the organophosphorus G- and V-type nerve agents and chemically related simulants (15 molecules ranging in size from 11 to 40 atoms); 21 other small molecules ranging in size from 8 to 24 atoms; and 13 proteins ranging in size from 304 to 11,352 atoms. Spectra for the first two sets of molecules were calculated using quantum chemistry software, the last two sets using force fields. The "middle" set used both methods, allowing for comparison between them and with experimental spectra from the NIST/EPA Gas-Phase Infrared Library. The calculated spectra of proteins, for which only force field calculations are practical, reproduced the experimentally observed amide I and II bands, but they were shifted by approximately +40 cm-1 relative to experiment. Considering the entire spectrum of protein vibrations, the most promising frequency range for differentiating between proteins was approximately 600-1300 cm-1 where water has low absorption and the proteins show some differences.
ContributorsMott, Adam J (Author) / Rez, Peter (Thesis advisor) / Ozkan, Banu (Committee member) / Shumway, John (Committee member) / Thorpe, Michael (Committee member) / Vaiana, Sara (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Sample delivery is an essential component in biological imaging using serial diffraction from X-ray Free Electron Lasers (XFEL) and synchrotrons. Recent developments have made possible the near-atomic resolution structure determination of several important proteins, including one G protein-coupled receptor (GPCR) drug target, whose structure could not easily have been

Sample delivery is an essential component in biological imaging using serial diffraction from X-ray Free Electron Lasers (XFEL) and synchrotrons. Recent developments have made possible the near-atomic resolution structure determination of several important proteins, including one G protein-coupled receptor (GPCR) drug target, whose structure could not easily have been determined otherwise (Appendix A). In this thesis I describe new sample delivery developments that are paramount to advancing this field beyond what has been accomplished to date. Soft Lithography was used to implement sample conservation in the Gas Dynamic Virtual Nozzle (GDVN). A PDMS/glass composite microfluidic injector was created and given the capability of millisecond fluidic switching of a GDVN liquid jet within the divergent section of a 2D Laval-like GDVN nozzle, providing a means of collecting sample between the pulses of current XFELs. An oil/water droplet immersion jet was prototyped that suspends small sample droplets within an oil jet such that the sample droplet frequency may match the XFEL pulse repetition rate. A similar device was designed to use gas bubbles for synchronized “on/off” jet behavior and for active micromixing. 3D printing based on 2-Photon Polymerization (2PP) was used to directly fabricate reproducible GDVN injectors at high resolution, introducing the possibility of systematic nozzle research and highly complex GDVN injectors. Viscous sample delivery using the “LCP injector” was improved with a method for dealing with poorly extruding sample mediums when using full beam transmission from the Linac Coherent Light Source (LCLS), and a new viscous crystal-carrying medium was characterized for use in both vacuum and atmospheric environments: high molecular weight Polyethylene Glycol.
ContributorsNelson, Garrett Charles (Author) / Spence, John C (Thesis advisor) / Weierstall, Uwe J (Thesis advisor) / Schmidt, Kevin E (Committee member) / Beckstein, Oliver (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Molecular docking serves as an important tool in modeling protein-ligand interactions. Most of the docking approaches treat the protein receptor as rigid and move the ligand in the binding pocket through an energy minimization, which is an incorrect approach as proteins are flexible and undergo conformational changes upon ligand binding.

Molecular docking serves as an important tool in modeling protein-ligand interactions. Most of the docking approaches treat the protein receptor as rigid and move the ligand in the binding pocket through an energy minimization, which is an incorrect approach as proteins are flexible and undergo conformational changes upon ligand binding. However, modeling receptor backbone flexibility in docking is challenging and computationally expensive due to the large conformational space that needs to be sampled.

A novel flexible docking approach called BP-Dock (Backbone Perturbation docking) was developed to overcome this challenge. BP-Dock integrates both backbone and side chain conformational changes of a protein through a multi-scale approach. In BP-Dock, the residues along a protein chain are perturbed mimicking the binding induced event, with a small Brownian kick, one at a time. The fluctuation response profile of the chain upon these perturbations is computed by Perturbation Response Scanning (PRS) to generate multiple receptor conformations for ensemble docking. To evaluate the performance of BP-Dock, this approach was applied to a large and diverse dataset of unbound structures as receptors. Furthermore, the protein-peptide docking of PICK1-PDZ proteins was investigated. This study elucidates the determinants of PICK1-PDZ binding that plays crucial roles in numerous neurodegenerative disorders. BP-Dock approach was also extended to the challenging problem of protein-glycan docking and applied to analyze the energetics of glycan recognition in Cyanovirin-N (CVN), a cyanobacterial lectin that inhibits HIV by binding to its highly glycosylated envelope protein gp120. This study provide the energetic contribution of the individual residues lining the binding pocket of CVN and explore the effect of structural flexibility in the hinge region of CVN on glycan binding, which are also verified experimentally. Overall, these successful applications of BP-Dock highlight the importance of modeling backbone flexibility in docking that can have important implications in defining the binding properties of protein-ligand interactions.

Finally, an induced fit docking approach called Adaptive BP-Dock is presented that allows both protein and ligand conformational sampling during the docking. Adaptive BP-Dock can provide a faster and efficient docking approach for the virtual screening of novel targets for rational drug design and aid our understanding of protein-ligand interactions.
ContributorsBolia, Ashini (Author) / Ozkan, Sefika Banu (Thesis advisor) / Ghirlanda, Giovanna (Thesis advisor) / Beckstein, Oliver (Committee member) / Wachter, Rebekka (Committee member) / Arizona State University (Publisher)
Created2015
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Description
In a typical living cell, millions to billions of proteins—nanomachines that fluctuate and cycle among many conformational states—convert available free energy into mechanochemical work. A fundamental goal of biophysics is to ascertain how 3D protein structures encode specific functions, such as catalyzing chemical reactions or transporting nutrients into a cell.

In a typical living cell, millions to billions of proteins—nanomachines that fluctuate and cycle among many conformational states—convert available free energy into mechanochemical work. A fundamental goal of biophysics is to ascertain how 3D protein structures encode specific functions, such as catalyzing chemical reactions or transporting nutrients into a cell. Protein dynamics span femtosecond timescales (i.e., covalent bond oscillations) to large conformational transition timescales in, and beyond, the millisecond regime (e.g., glucose transport across a phospholipid bilayer). Actual transition events are fast but rare, occurring orders of magnitude faster than typical metastable equilibrium waiting times. Equilibrium molecular dynamics (EqMD) can capture atomistic detail and solute-solvent interactions, but even microseconds of sampling attainable nowadays still falls orders of magnitude short of transition timescales, especially for large systems, rendering observations of such "rare events" difficult or effectively impossible.

Advanced path-sampling methods exploit reduced physical models or biasing to produce plausible transitions while balancing accuracy and efficiency, but quantifying their accuracy relative to other numerical and experimental data has been challenging. Indeed, new horizons in elucidating protein function necessitate that present methodologies be revised to more seamlessly and quantitatively integrate a spectrum of methods, both numerical and experimental. In this dissertation, experimental and computational methods are put into perspective using the enzyme adenylate kinase (AdK) as an illustrative example. We introduce Path Similarity Analysis (PSA)—an integrative computational framework developed to quantify transition path similarity. PSA not only reliably distinguished AdK transitions by the originating method, but also traced pathway differences between two methods back to charge-charge interactions (neglected by the stereochemical model, but not the all-atom force field) in several conserved salt bridges. Cryo-electron microscopy maps of the transporter Bor1p are directly incorporated into EqMD simulations using MD flexible fitting to produce viable structural models and infer a plausible transport mechanism. Conforming to the theme of integration, a short compendium of an exploratory project—developing a hybrid atomistic-continuum method—is presented, including initial results and a novel fluctuating hydrodynamics model and corresponding numerical code.
ContributorsSeyler, Sean L (Author) / Beckstein, Oliver (Thesis advisor) / Chamberlin, Ralph (Committee member) / Matyushov, Dmitry (Committee member) / Thorpe, Michael F (Committee member) / Vaiana, Sara (Committee member) / Arizona State University (Publisher)
Created2017
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Description
In this dissertation two kinds of strongly interacting fermionic systems were studied: cold atomic gases and nucleon systems. In the first part I report T=0 diffusion Monte Carlo results for the ground-state and vortex excitation of unpolarized spin-1/2 fermions in a two-dimensional disk. I investigate how vortex core structure properties

In this dissertation two kinds of strongly interacting fermionic systems were studied: cold atomic gases and nucleon systems. In the first part I report T=0 diffusion Monte Carlo results for the ground-state and vortex excitation of unpolarized spin-1/2 fermions in a two-dimensional disk. I investigate how vortex core structure properties behave over the BEC-BCS crossover. The vortex excitation energy, density profiles, and vortex core properties related to the current are calculated. A density suppression at the vortex core on the BCS side of the crossover and a depleted core on the BEC limit is found. Size-effect dependencies in the disk geometry were carefully studied. In the second part of this dissertation I turn my attention to a very interesting problem in nuclear physics. In most simulations of nonrelativistic nuclear systems, the wave functions are found by solving the many-body Schrödinger equations, and they describe the quantum-mechanical amplitudes of the nucleonic degrees of freedom. In those simulations the pionic contributions are encoded in nuclear potentials and electroweak currents, and they determine the low-momentum behavior. By contrast, in this work I present a novel quantum Monte Carlo formalism in which both relativistic pions and nonrelativistic nucleons are explicitly included in the quantum-mechanical states of the system. I report the renormalization of the nucleon mass as a function of the momentum cutoff, an Euclidean time density correlation function that deals with the short-time nucleon diffusion, and the pion cloud density and momentum distributions. In the two nucleon sector the interaction of two static nucleons at large distances reduces to the one-pion exchange potential, and I fit the low-energy constants of the contact interactions to reproduce the binding energy of the deuteron and two neutrons in finite volumes. I conclude by showing that the method can be readily applied to light-nuclei.
ContributorsMadeira, Lucas (Author) / Schmidt, Kevin E (Thesis advisor) / Alarcon, Ricardo (Committee member) / Beckstein, Oliver (Committee member) / Erten, Onur (Committee member) / Arizona State University (Publisher)
Created2018
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Description
The structure of glass has been the subject of many studies, however some

details remained to be resolved. With the advancement of microscopic

imaging techniques and the successful synthesis of two-dimensional materials,

images of two-dimensional glasses (bilayers of silica) are now available,

confirming that this glass structure closely follows the continuous random

network model. These

The structure of glass has been the subject of many studies, however some

details remained to be resolved. With the advancement of microscopic

imaging techniques and the successful synthesis of two-dimensional materials,

images of two-dimensional glasses (bilayers of silica) are now available,

confirming that this glass structure closely follows the continuous random

network model. These images provide complete in-plane structural information

such as ring correlations, and intermediate range order and with computer

refinement contain indirect information such as angular distributions, and

tilting.

This dissertation reports the first work that integrates the actual atomic

coordinates obtained from such images with structural refinement to enhance

the extracted information from the experimental data.

The correlations in the ring structure of silica bilayers are studied

and it is shown that short-range and intermediate-range order exist in such networks.

Special boundary conditions for finite experimental samples are designed so atoms

in the bulk sense they are part of an infinite network.

It is shown that bilayers consist of two identical layers separated by a

symmetry plane and the tilted tetrahedra, two examples of

added value through the structural refinement.

Finally, the low-temperature properties of glasses in two dimensions

are studied. This dissertation presents a new approach to find possible

two-level systems in silica bilayers employing the tools of rigidity theory

in isostatic systems.
ContributorsSadjadi, Seyed Mahdi (Author) / Thorpe, Michael F (Thesis advisor) / Beckstein, Oliver (Committee member) / Schmidt, Kevin E (Committee member) / Treacy, Michael Mj (Committee member) / Arizona State University (Publisher)
Created2018
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Description
The rigidity of a material is the property that enables it to preserve its structure when deformed. In a rigid body, no internal motion is possible since the degrees of freedom of the system are limited to translations and rotations only. In the macroscopic scale, the rigidity and response of

The rigidity of a material is the property that enables it to preserve its structure when deformed. In a rigid body, no internal motion is possible since the degrees of freedom of the system are limited to translations and rotations only. In the macroscopic scale, the rigidity and response of a material to external load can be studied using continuum elasticity theory. But when it comes to the microscopic scale, a simple yet powerful approach is to model the structure of the material and its interparticle interactions as a ball$-$and$-$spring network. This model allows a full description of rigidity in terms of the vibrational modes and the balance between degrees of freedom and constraints in the system.

In the present work, we aim to establish a microscopic description of rigidity in \emph{disordered} networks. The studied networks can be designed to have a specific number of degrees of freedom and/or elastic properties. We first look into the rigidity transition in three types of networks including randomly diluted triangular networks, stress diluted triangular networks and jammed networks. It appears that the rigidity and linear response of these three types of systems are significantly different. In particular, jammed networks display higher levels of self-organization and a non-zero bulk modulus near the transition point. This is a unique set of properties that have not been observed in any other types of disordered networks. We incorporate these properties into a new definition of jamming that requires a network to hold one extra constraint in excess of isostaticity and have a finite non-zero bulk modulus. We then follow this definition by using a tuning by pruning algorithm to build spring networks that have both these properties and show that they behave exactly like jammed networks. We finally step into designing new disordered materials with desired elastic properties and show how disordered auxetic materials with a fully convex geometry can be produced.
ContributorsFaghir Hagh, Varda (Author) / Thorpe, Michael F. (Thesis advisor) / Beckstein, Oliver (Committee member) / Chamberlin, Ralph V. (Committee member) / Schmidt, kevin E. (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Bio-molecules and proteins are building blocks of life as is known, and understanding

their dynamics and functions are necessary to better understand life and improve its

quality. While ergodicity and fluctuation dissipation theorem (FDT) are fundamental

and crucial concepts regarding study of dynamics of systems in equilibrium, biological

function is not possible in equilibrium.

In

Bio-molecules and proteins are building blocks of life as is known, and understanding

their dynamics and functions are necessary to better understand life and improve its

quality. While ergodicity and fluctuation dissipation theorem (FDT) are fundamental

and crucial concepts regarding study of dynamics of systems in equilibrium, biological

function is not possible in equilibrium.

In this work, dynamical and orientational structural crossovers in low-temperature

glycerol are investigated. A sudden and notable increase in the orientational Kirk-

wood factor and the dielectric constant is observed, which appears in the same range

of temperatures that dynamic crossover of translational and rotational dynamics oc-

cur.

Theory and electrochemistry of cytochrome c is also investigated. The seeming

discrepancy in reorganization energies of protein electron transfer produced by atom-

istic simulations and those reported by protein electrochemistry (which are smaller)

is resolved. It is proposed in this thesis that ergodicity breaking results in an effective

reorganization energy (0.57 eV) consistent with experiment.

Ergodicity breaking also affects the iron displacement in heme proteins. A model

for dynamical transition of atomic displacements in proteins is provided. Different

temperatures for rotational and translational crossovers of water molecules are re-

ported, which all are ergodicity breaking transitions depending on the corresponding

observation windows. The comparison with Mössbauer spectroscopy is presented.

Biological function at low temperatures and its termination is also investigated in

this research. Here, it is proposed that ergodicity breaking gives rise to the violation

of the FDT, and this violation is maintained in the entire range of physiological

temperatures for cytochrome c. Below the crossover temperature, the protein returns

to the FDT, which leads to a sudden jump in the activation barrier for electron

itransfer.

Finally the interaction of charges in dielectric materials is discussed. It is shown

that the potential of mean force between ions in polar liquids becomes oscillatory at

short distances.
ContributorsSeyedi, seyed salman (Author) / Matyushov, Dmitry V (Thesis advisor) / Beckstein, Oliver (Committee member) / Vaiana, Sara M (Committee member) / Ros, Robert (Committee member) / Arizona State University (Publisher)
Created2018