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Physics 422 Spring 2023 Syllabus - Medical Physics, Ronald Koder

Open Educational Resources

This is the Spring 2023 syllabus for Physics 315, Medical Physics, at CCNY

Physics 422 Spring 2023 Syllabus, Ronald Koder

Open Educational Resources

Spring 2023 course syllabus for Physics 422, Biophysics, at the City College of New York

Raw Data Files For The Manuscript 'Elastin Recoil Is Driven By The Hydrophobic Effect', Nour M. Jamhawi, Ronald Koder, Richard J. Wittebort

Publications and Research

These are the raw data files associated with the manuscript 'Elastin Recoil is Driven by the Hydrophobic Effect' by Nour M. Jamhawi, Ronald L. Koder, and Richard J. Wittebort

Symmetry-Inspired Analysis Of Biological Networks, Ian Leifer

Dissertations, Theses, and Capstone Projects

The description of a complex system like gene regulation of a cell or a brain of an animal in terms of the dynamics of each individual element is an insurmountable task due to the complexity of interactions and the scores of associated parameters. Recent decades brought about the description of these systems that employs network models. In such models the entire system is represented by a graph encapsulating a set of independently functioning objects and their interactions. This creates a level of abstraction that makes the analysis of such large scale system possible. Common practice is to draw conclusions about …

Eukaryotic Initiation Factor 4e (Eif4e) In Complex With Eif4e Binding Protein 1 (4e-Bp1) Binds With Higher Affinity To M7gpppn Cap Of A Subset Of Human Mrnas, Izza F. Nawaz

Theses and Dissertations

Fluorescence anisotropy binding assays were used to analyze the binding of eIF4E in complex with 4E-BP1 onto the 5’ m7G cap of a subset of mRNA that are known to carry cap-independent translation. These studies suggest that 4E-BP1 increases eIF4E binding affinity to 5’cap of both FGF-9 and HIF-1𝝰.

Paddling Along The Voltage Gated Sodium Channel Galaxy With Sea Anemone Toxins: Structural Studies Of The Interaction Between The Paddle Motif From Nav1.5div And Sea Anemone Toxin, Adel K. Hussein

Dissertations, Theses, and Capstone Projects

Voltage gated sodium channels (VGSC) are membrane proteins that serve an important function in the central nervous system (CNS), peripheral nervous system (PNS), and cardiac muscles amongst others. The main function of VGSC is in the propagation of electrical signals by depolarizing excitable cells. Nine mammalian VGSC subtypes have been characterized, Na_V1.1 – Na_V1.9, that are expressed in a tissue specific manner, each with unique gating properties. Numerous diseases have been linked to defects in VGSC including epilepsy, mental retardation, long QT syndrome, and Brugada disease. Furthermore, these channels are one of the primary targets of …

Structural And Biochemical Investigations Of The Initiation Of Dna Replication In Bacteriophage Lambda And Escherichia Coli, Jillian D. Chase

Dissertations, Theses, and Capstone Projects

Faithful transmission of genetic information is requisite for the propagation of all life. DNA replication in each of the three domains of life requires the separation of double stranded DNA (dsDNA) into single stranded DNA (ssDNA) which then serves as a template for genomic duplication of each original DNA strand. Initiation of replication events occurs by tightly regulated processes during which specialized proteins are loaded at a specific locus within the genome, termed the origin of replication, in preparation of bidirectional replication events. A replicative helicase must be loaded or assembled on both strands of DNA at the origin to …

Water-Based Lead Generation, Brian Olson

Dissertations, Theses, and Capstone Projects

Water-based Lead Generation. The opioid epidemic and the SARS-CoV-2 pandemic are current serious challenges whose devastating effects could be assuaged through the development of new drugs. Opioids that are functional painkillers, that are less likely to cause overdose, and small molecule drugs that could inhibit the life cycle of SARS-CoV-2 would be useful. The work herein investigated the use of water molecules for lead generation in drug development against opioid receptors and SARS-CoV-2 viral proteins. In opioid receptor binding sites, purported bridging waters were obtained from crystal waters or from molecular dynamics simulations, as Hydration Site Analysis was used to …

High-Resolution Cryo-Electron Microscopy Structure Of Photosystem Ii From The Mesophilic Cyanobacterium, Synechocystis Sp. Pcc 6803, Christopher J. Gisriel, Jimin Wang, Jinchan Liu, David A. Flesher, Krystle M. Reiss, Hao-Li Huang, Ke R. Yang, William H. Armstrong, M. R. Gunner, Victor S. Batista, Richard J. Debus, Gary W. Brudvig

Publications and Research

Photosystem II (PSII) enables global-scale, light-driven water oxidation. Genetic manipulation of PSII from the mesophilic cyanobacterium Synechocystis sp. PCC 6803 has provided insights into the mechanism of water oxidation; however, the lack of a highresolution structure of oxygen-evolving PSII from this organism has limited the interpretation of biophysical data to models based on structures of thermophilic cyanobacterial PSII. Here, we report the cryo-electron microscopy structure of PSII from Synechocystis sp. PCC 6803 at 1.93-Å resolution. A number of differences are observed relative to thermophilic PSII structures, including the following: the extrinsic subunit PsbQ is maintained, the C terminus of the …

Structure Of A Monomeric Photosystem Ii Core Complex From A Cyanobacterium Acclimated To Far-Red Light Reveals The Functions Of Chlorophylls D And F, Christopher J. Gisriel, Gaozhong Shen, Ming-Yang Ho, Vasily Kurashov, David A. Flesher, Jimin Wang, William H. Armstrong, John H. Golbeck, Marilyn R. Gunner, David J. Vinyard, Richard J. Debus, Gary W. Brudvig, Donald A. Bryant

Publications and Research

Far-red light (FRL) photoacclimation in cyanobacteria provides a selective growth advantage for some terrestrial cyanobacteria by expanding the range of photosynthetically active radiation to include far-red/near-infrared light (700–800 nm). During this photoacclimation process, photosystem II (PSII), the water:plastoquinone photooxidoreductase involved in oxygenic photosynthesis, is modified. The resulting FRL-PSII is comprised of FRL-specific core subunits and binds chlorophyll (Chl) d and Chl f molecules in place of several of the Chl a molecules found when cells are grown in visible light. These new Chls effectively lower the energy canonically thought to define the “red limit” for light required to drive photochemical …

Machine Learning And Solvation Theory For Drug Discovery, Lieyang Chen

Dissertations, Theses, and Capstone Projects

Drug discovery is a notoriously expensive and time-consuming process; hence, developing computational methods to facilitate the discovery process and lower the associated costs is a long-sought goal of computational chemists. Protein-ligand binding, which provides the physical and chemical basis for the mechanism of action of most drugs, occurs in an aqueous environment, and binding affinity is determined not only by atomic interactions between the protein and ligand but also by changes in their interactions with surrounding water molecules that occur upon binding. Thus, a quantitative understanding of the roles water molecules play in the protein-ligand binding process is an essential …

Dual Control Of One Component Signaling: Mechanistic And Structural Insights Into El222 Active States, Uthama Phani R. Edupuganti

Dissertations, Theses, and Capstone Projects

Photoreceptors play a crucial role in signal transduction as specialized proteins which sense light as environmental stimuli and transduce the signal to control of downstream functions. Here we focus our attention on one class of these proteins, the Light-Oxygen-Voltage (LOV) domain, which is sensitive to blue light via an internally-bound flavin chromophore. Since their initial discovery in plant phototropins, many details of their photochemistry, chromophore interactions, and use with a diverse set of functional effectors have been described. However, several key details, especially a comprehensive understanding of signaling mechanism and its regulation, still remain elusive due in part to the …

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber

Dissertations, Theses, and Capstone Projects

Light provides organisms with energy and spatiotemporal information. To survive and adapt, organisms have developed the ability to sense light to drive biochemical effects that underlie vision, entrainment of circadian rhythm, stress response, virulence, and many other important molecularly driven responses. Blue-light sensing Light-Oxygen-Voltage (LOV) domains are ubiquitous across multiple kingdoms of life and modulate various physiological events via diverse effector domains. Using a small molecule flavin chromophore, the LOV domain undergoes light-dependent structural changes leading to activation or repression of these catalytic and non-catalytic effectors. In silico analyses of high-throughput genomic sequencing data has led to the marked expansion …

Computational Modeling Of Water And Proteins In Drug Discovery, Anthony Cruz Balberdy

Dissertations, Theses, and Capstone Projects

This thesis aims to improve how structural and thermodynamic properties of water on protein surfaces can be exploited to aid early stage drug discovery and lead optimization. We first discuss our development of SSTMap, a public domain software suite that maps out the properties of water on biomolecular surfaces. We then show the utility of these maps in describing differences in binding affinities between congeneric pairs of ligands. We then discuss our use of solvation maps in the prospective discovery of novel binders to cytochrome C peroxidase. Finally, we present our creation and validation of a homology model of Interleukin-24 …

Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex, Michael Redlich

Dissertations, Theses, and Capstone Projects

Here we present the use of Third Harmonic Generation (THG) for the label-free imaging of myelinated axons in the murine cerebral cortex. Myelin plays an important role in the processes of learning and disease. However, much of the myelin biology research thus far has focused on white matter tracts where myelin is more visible. Much is still unknown, particularly with regard to myelin in gray matter. First, we engage in THG microscopy using an optical parametric oscillator pumped by a titanium-sapphire laser to demonstrate the utility of the technique for imaging myelin in vivo. Second, we investigate the use of …

The C. Neoformans Cell Wall: A Scaffold For Virulence, Christine Chrissian

Dissertations, Theses, and Capstone Projects

Cryptococcus neoformans is a globally distributed opportunistic fungal pathogen and the causative agent of life threatening cryptococcal meningoencephalitis in immunocompromised individuals, resulting in ~180,000 deaths each year worldwide. A primary virulence-associated trait of this organism is the production of melanin. Melanins are a class of diverse pigments produced via the oxidation and polymerization of aromatic ring compounds that have a characteristically complex, heterogenous, and amorphous structure. They are synthesized by representatives of all biological kingdoms and share a multitude of remarkable properties such as the ability to absorb ultraviolet (UV) light and protect against ionizing radiation. Melanin production in fungi …

Direct Recruitment Of Eif4gi And/Dap5 To The 5' Utr Of A Subset Of Human Mrna Drives Their Cap-Independent Translation, Solomon A. Haizel

Dissertations, Theses, and Capstone Projects

During unfavorable cellular conditions (e.g., tumor hypoxia, viral infection, nutrient deprivation, etc.), the canonical, cap-dependent translation initiation pathway in human cells is suppressed by sequestration of the cap-binding protein, eukaryotic initiation factor(eIF) 4E, by 4E-binding proteins. Circumvention of cap-dependent translation shutdown has been linked to tumor development and cancer progression. The stress-induced repression of cap-dependent translation has also been correlated with increased eIF4GI and its homolog, Death Associated Protein 5 (DAP5) expression levels, suggesting these factors have a role in cap-independent translation. Despite several evidence pointing towards a link upregulation of eIF4GI and /DAP5 levels during stress conditions, and the …

Using The Marcus Inverted Region And Artificial Cofactors To Create A Charge Separated State In De Novo Designed Proteins, Eskil Me Andersen

Dissertations, Theses, and Capstone Projects

To create an efficient de novo photosynthetic protein it is important to create long lived charge separated states. Achieving stable charge separation leads to an increase in the efficiency of the photosynthetic reaction which in turn leads to higher yields of end products, such as biofuels, electrical charge, or synthetic chemicals. In an attempt to create charge separated states in de novo proteins we hypothesized that we could engineer the free energy gaps in the proteins from excited primary donor (PD) to acceptor (A), and A back to ground state PD such that the forward electron transfer (ET) would be …

Retrieving Functional Pathways Of Biomolecules From Single-Particle Snapshots, Ali Dashti, Ghoncheh Mashayekhi, Mrinal Shekhar, Danya Ben Hail, Salah Salah, Peter Schwander, Amedee Des Georges, Abhishek Singharoy, Joachim Frank, Abbas Ourmazd

Publications and Research

A primary reason for the intense interest in structural biology is the fact that knowledge of structure can elucidate macromolecular functions in living organisms. Sustained effort has resulted in an impressive arsenal of tools for determining the static structures. But under physiological conditions, macromolecules undergo continuous conformational changes, a subset of which are functionally important. Techniques for capturing the continuous conformational changes underlying function are essential for further progress. Here, we present chemically-detailed conformational movies of biological function, extracted data-analytically from experimental single-particle cryo-electron microscopy (cryo-EM) snapshots of ryanodine receptor type 1 (RyR1), a calcium-activated calcium channel engaged in the …

Snow-Albedo Feedback In Northern Alaska: How Vegetation Influences Snowmelt, Lucas C. Reckhaus

Theses and Dissertations

This paper investigates how the snow-albedo feedback mechanism of the arctic is changing in response to rising climate temperatures. Specifically, the interplay of vegetation and snowmelt, and how these two variables can be correlated. This has the potential to refine climate modelling of the spring transition season. Research was conducted at the ecoregion scale in northern Alaska from 2000 to 2020. Each ecoregion is defined by distinct topographic and ecological conditions, allowing for meaningful contrast between the patterns of spring albedo transition across surface conditions and vegetation types. The five most northerly ecoregions of Alaska are chosen as they encompass …

Circuits With Broken Fibration Symmetries Perform Core Logic Computations In Biological Networks, Ian Leifer, Flaviano Morone, Saulo D. S. Reis, José S. Andrade Jr., Mariano Sigman, Hernán A. Makse

Publications and Research

We show that logic computational circuits in gene regulatory networks arise from a fibration symmetry breaking in the network structure. From this idea we implement a constructive procedure that reveals a hierarchy of genetic circuits, ubiquitous across species, that are surprising analogues to the emblematic circuits of solid-state electronics: starting from the transistor and progressing to ring oscillators, current-mirror circuits to toggle switches and flip-flops. These canonical variants serve fundamental operations of synchronization and clocks (in their symmetric states) and memory storage (in their broken symmetry states). These conclusions introduce a theoretically principled strategy to search for computational building blocks …

Dna Damage Recognition And Uvrb Loading By Uvra Within The Nucleotide Excision Repair Pathway, Silas Hartley

Dissertations, Theses, and Capstone Projects

Maintaining the cellular genome is paramount to survival by any organism. A mutated genome can have detrimental effects on different cellular processes, especially replication and transcription. Cells maintain their genome using different deoxyribonucleic acid (DNA) repair pathways. The nucleotide excision repair (NER) pathway has a unique capability of repairing the genome from several different mutations, deletions, and adducts. In bacteria, the NER pathway accomplishes repair through four important steps: damage recognition by UvrA, damage verification by UvrB, DNA incision by UvrC, and repair synthesis using various cellular machinery.

UvrA forms a head-to-head dimer (UvrA₂) with two ATPase sites …

Proton Pumping Mechanism In Cytochrome C Oxidase, Xiuhong Cai

Dissertations, Theses, and Capstone Projects

Cytochrome c Oxidase (CcO), is the terminal electron acceptor in the membrane bound aerobic respiratory chain. It reduces O₂ to water. The energy released by this reaction is stored by pumping protons from the high pH, N-side of the membrane to the low pH, P-side. The generated proton gradient provides the motive force for synthesis of ATP by the ATP synthase.

Building a proton gradient across the membrane requires that proton transport must occur along controllable proton pathways to prevent proton leakage to the N-side. It has been suggested that CcO function requires proton transfer channels in both the …

Fibration Symmetries Uncover The Building Blocks Of Biological Networks, Flaviano Morone, Ian Leifer, Hernán A. Makse

Publications and Research

A major ambition of systems science is to uncover the building blocks of any biological network to decipher how cellular function emerges from their interactions. Here, we introduce a graph representation of the information flow in these networks as a set of input trees, one for each node, which contains all pathways along which information can be transmitted in the network. In this representation, we find remarkable symmetries in the input trees that deconstruct the network into functional building blocks called fibers. Nodes in a fiber have isomorphic input trees and thus process equivalent dynamics and synchronize their activity. Each …

Advanced Computational Methodologies To Study Binding Free Energies Of Biomolecular Complexes, Rajat Kumar Pal

Dissertations, Theses, and Capstone Projects

Molecular recognition is the basis of biological mechanisms and is a key element to consider while formulating effective and safe drugs. Pharmaceutical drugs are designed so as to bind a target protein even at very low concentrations to alter the diseased conditions without interfering with normal biological processes. In a rational drug design process, this is achieved by acquiring information about the chemical structure and the physical and chemical properties of the target protein receptor to gain insights on how changing the chemical composition of the substrate drug could affect the protein-drug interaction and binding affinities. Computational models are used …

Minimalistic Peptide-Based Supramolecular Systems Relevant To The Chemical Origin Of Life, Daniela Kroiss

Dissertations, Theses, and Capstone Projects

All forms of life are based on biopolymers, which are made up of a selection of simple building blocks, such as amino acids, nucleotides, fatty acids and sugars. Their individual properties govern their interactions, giving rise to complex supramolecular structures with highly specialized functionality, including ligand recognition, catalysis and compartmentalization. In this thesis, we aim to answer the question whether short peptides could have acted as precursors of modern proteins during prebiotic evolution. Using a combination of experimental and computational techniques, we screened a large molecular search space for peptide sequences that are capable of forming supramolecular complexes with adenosine …

Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly

Dissertations, Theses, and Capstone Projects

The potency and specificity of bioactive peptides have propelled these agents to the forefront of pharmacological research. However, delivery of peptides to their molecular target in cells is a major obstacle to their widespread application. A Trojan Horse strategy of packaging a bioactive peptide within a modified protein cage to protect it during transport, and releasing it at the target site, is a promising delivery method. Recent work has demonstrated that the viral capsid of the P22 bacteriophage can be loaded with an arbitrary, genetically-encoded peptide, and externally decorated with a cell-penetrating peptide, such as HIV-Tat, to translocate across in …

Hyaluronan At The Brain-Environment Interface, Donald M. Thevalingam

Dissertations, Theses, and Capstone Projects

Hyaluronan (HA; Hyaluronic Acid), a primary scaffolding component of the brain extracellular matrix, serves as an integral structural component to the brain extracellular space (ECS). The fossorial African naked mole-rat (Heterocephalus glaber; NM-R), a mammal which lives in a low-oxygen environment and is capable of tolerating hypoxia and hypercapnia, has been shown to synthesize and sustain a unique high-molecular-mass variant of hyaluronan macromolecule (HMM-HA). This body of work highlights HA’s role in mediating the interplay between brain ECM composition, ECS structure, and cell viability.

Here we employ the NM-R as a unique animal model to observe the role of the …

Characterization Of Early Biofilm Formation And Physiology In Neisseria Gonorrhoeae, Kelly Eckenrode

Dissertations, Theses, and Capstone Projects

Many bacteria rely on the dynamics of their extracellular appendages to perform important tasks, like motility and biofilm formation. Interestingly, these dynamics have been linked to physiological responses in some pathogenic bacteria; therefore, it is important to understand more about the role of physical forces in bacteria. I used the causative agent of the human disease gonorrhea, Neisseria gonorrhoeae, as a model system to study the role of physical force on early biofilm formation. The advantage of this system is that cell-cell interactions are controlled by extracellular filaments called type IV pili (tfp). Tfp is composed of monomers that give …