Physical Sciences and Mathematics Commons^™

Modeling Accuracy Matters: Aligning Molecular Dynamics With 2d Nmr Derived Noe Restraints, Milan Patel

Honors Scholar Theses

Among structural biology techniques, Nuclear Magnetic Resonance (NMR) provides a holistic view of structure that is close to protein structure in situ. Namely, NMR imaging allows for the solution state of the protein to be observed, derived from Nuclear Overhauser Effect restraints (NOEs). NOEs are a distance range in which hydrogen pairs are observed to stay within range of, and therefore experimental data which computational models can be compared against. To that end, we investigated the effects of adding the NOE restraints as distance restraints in Molecular Dynamics (MD) simulations on the 24 residue HP24stab derived villin headpiece subdomain to …

A Pipeline To Generate Deep Learning Surrogates Of Genome-Scale Metabolic Models, Achilles Rasquinha

Department of Computer Science and Engineering: Dissertations, Theses, and Student Research

Genome-Scale Metabolic Models (GEMMs) are powerful reconstructions of biological systems that help metabolic engineers understand and predict growth conditions subjected to various environmental factors around the cellular metabolism of an organism in observation, purely in silico. Applications of metabolic engineering range from perturbation analysis and drug-target discovery to predicting growth rates of biotechnologically important metabolites and reaction objectives within dierent single-cell and multi-cellular organism types. GEMMs use mathematical frameworks for quantitative estimations of flux distributions within metabolic networks. The reasons behind why an organism activates, stuns, or fluctuates between alternative pathways for growth and survival, however, remain relatively unknown. GEMMs …

The Role Of Conformational Changes In Viral And Bacterial Protein Functions, Md Lokman Hossen

FIU Electronic Theses and Dissertations

Proteins do versatile work in cells. They require a cascade of structural changes to perform different tasks like binding to the other neighboring biomolecules, transporting small chemicals, activating a chemical reaction, etc. The structural conformations of proteins can be critical in changing their working ability. In this dissertation, I investigated the role of conformational changes of viral protein, e.g., spike and envelope protein of SARS-CoV-2, and bacterial protein, e.g., multidrug transporter and toxic extrusion protein- PfMATE from Pyrococcus furiosus. Also, I performed molecular docking-based drug screening targeting the E protein to suggest a set of drugs that can be repurposed …

Foldamers Reveal And Validate Therapeutic Targets Associated With Toxic Α-Synuclein Self-Assembly, Jemil Ahmed, Tessa C. Fitch, Courtney M. Donnelly, Johnson A. Joseph, Tyler D. Ball, Mikaela M. Bassil, Ahyun Son, Chen Zhang, Aurélie Ledreux, Scott Horowitz, Yan Qin, Daniel Paredes, Sunil Kumar

Chemistry and Biochemistry: Faculty Scholarship

Parkinson’s disease (PD) is a progressive neurodegenerative disorder for which there is no successful prevention or intervention. The pathological hallmark for PD involves the self-assembly of functional Alpha-Synuclein (αS) into non-functional amyloid structures. One of the potential therapeutic interventions against PD is the effective inhibition of αS aggregation. However, the bottleneck towards achieving this goal is the identification of αS domains/sequences that are essential for aggregation. Using a protein mimetic approach, we have identified αS sequences-based targets that are essential for aggregation and will have significant therapeutic implications. An extensive array of in vitro, ex vivo, and in vivo assays …

The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen

CSB and SJU Distinguished Thesis

An unexpected outbreak of SARS-CoV-2 caused a worldwide pandemic in 2020. Many repurposed drugs were tested, but there are currently only three FDA approved antivirals (Merck’s antiviral Molnupiravir, Pfizer’s antiviral Paxlovid, and Remdisivir).1 Most of the antiviral drugs tested SARS-CoV-2 main protease and RNA-dependent RNA polymerase. However, it is important to explore different drug targets of SARS-CoV-2 to prepare for the virus mutations of the future. This research looks at an alternative approach in which SARSCoV- 2 Open Reading Frame 8 (ORF8), which has been shown to be a rapidly evolving hypervariable gene, was chosen to be the protein of …

Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, Jacob Minkkinen

CSB and SJU Distinguished Thesis

Severe acute respiratory syndrome (SARS-CoV-2) led to the COVID-19 global pandemic, with over 460 million cases of infection and over 6 million deaths since the start of the pandemic. SARS-CoV-2 is a retrovirus that utilizes a main protease (Mpro). Mpro is a catalytic cys/his protease. Several treatments were proposed to stop the pandemic including repurposing drugs to inhibit the Mpro. Another retrovirus that uses a protease is human immunodeficiency virus (HIV-1) which has been a global epidemic for 40 years and is a devastating disease that attacks the immune system. HIV-1 has infected 79.5 million people and has killed an …

Awegnn: Auto-Parametrized Weighted Element-Specific Graph Neural Networks For Molecules., Timothy Szocinski, Duc Duy Nguyen, Guo-Wei Wei

Mathematics Faculty Publications

While automated feature extraction has had tremendous success in many deep learning algorithms for image analysis and natural language processing, it does not work well for data involving complex internal structures, such as molecules. Data representations via advanced mathematics, including algebraic topology, differential geometry, and graph theory, have demonstrated superiority in a variety of biomolecular applications, however, their performance is often dependent on manual parametrization. This work introduces the auto-parametrized weighted element-specific graph neural network, dubbed AweGNN, to overcome the obstacle of this tedious parametrization process while also being a suitable technique for automated feature extraction on these internally complex …

"Flagella Base Model" And "Flagellin Monomer", Brandon Lasalle, Rebecca Roston

3-D Printed Model Structural Files

"Flagella Base Model" and "Flagellin monomer"

Description: This is a teaching model of the proteins that make a bacterial flagella. All models are depicted in space-fill. The Flagellin monomer and the Flagella base can slot together to show protein quaternary structure and filamentous protein assembly.

Printable models are already uploaded to Shapeways.com in the MacroMolecules shop under the names "Flagella Base Model" and "Flagellin monomer".

This model has been printed successfully using these parameters on Shapeways’ laser sintering printer in the following material: Processed Versatile Plastic (Strong & Flexible Plastic).

Model designer: Brandon Lasalle Authors: Brandon Lasalle and Rebecca Roston …

Amino Acid Pop-Set: Model File Name: Amino-Acid-Wgrp-Pop_Sc3.Stl, Michelle Howell, Rebecca Roston

3-D Printed Model Structural Files

This is a teaching model for protein primary structure. It consists of four amino acids (tryptophan, proline, arginine, and glycine) depicted in stick and space-fill representations, five peptide bonds depicted in space-fill, and an N-terminus and a C-terminus depicted in space-fill. It is designed so that students can make various peptides to explore the amount of space of the electron clouds of the amino acids and bonds, and explore the psi and phi angles for the peptides. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Amino acid pop-set”. This model has …

Lipoprotein Signal Peptidase Ii: Model File Name: 5dir-Lipoii-Reps_Sc1-5.Stl, Michelle Howell, Rebecca Roston

3-D Printed Model Structural Files

This is a teaching model of lipoprotein signal peptidase II (PDB: 5DIR). It is designed with different regions of the protein depicted in space-filling, ribbon, stick, and backbone-only representations to explore protein secondary structure and illustrate how much space the protein takes up. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Lipoprotein signal peptidase II” and is intended to accompany the “Crambin”, “Cytochrome c” and “3 water molecules” models. This model has been printed successfully using these parameters on Shapeways’ laser sintering printer in …

3 Water Molecules: Model File Name: 3hoh-Final.Stl, Michelle Howell, Rebecca Roston

3-D Printed Model Structural Files

This is a teaching model of 3 water molecules depicted in space-fill. It is designed to the same scale as the “Lipoprotein signal peptidase II”, “Crambin”, and “Cytochrome c” models to illustrate the amount of space taken up by proteins. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “3 water molecules” and is intended to accompany the “Lipoprotein signal peptidase II”, “Crambin”, and “Cytochrome c” models. This model has been printed successfully using these parameters on Shapeways’ laser sintering …

Crambin: Model File Name: 2fd7-Crambin-Stick_Sc1-5.Stl, Michelle Howell, Rebecca Roston

3-D Printed Model Structural Files

This is a teaching model of cytochrome c (PDB: 2FD7). It is designed in a stick representation to explore protein secondary structure and how much space the protein takes up. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Crambin” and is intended to accompany the “Lipoprotein signal peptidase II”, “Cytochrome c”, and “3 water molecules” models. This model has been printed successfully using these parameters on Shapeways’ laser sintering printer in the following material: Processed Versatile Plastic (Strong & Flexible Plastic).

Cytochrome C: Model File Name: 1b7v-Cytc-Stick_Sc1-5.Stl, Michelle Howell, Rebecca Roston

3-D Printed Model Structural Files

This is a teaching model of cytochrome c (PDB: 1B7V). It is designed in a stick representation to explore protein secondary structure and how much space the protein takes up. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Cytochrome c” and is intended to accompany the “Lipoprotein signal peptidase II”, “Crambin”, and “3 water molecules” models. This model has been printed successfully using these parameters on Shapeways’ laser sintering printer in the following material: Processed Versatile Plastic (Strong & Flexible Plastic).

Human Hexokinase I - Allosteric Regulation: Model File Name: 1dgk-Editb22-Allostery_Sc06.Stl, Michelle Howell, Rebecca Roston

3-D Printed Model Structural Files

This is a teaching model of human Hexokinase I in a surface representation with small molecules ADP and G6P included (PDB: 1DGK). It is designed to be hollow with a lever to mimic allosteric regulation. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Human Hexokinase I - Allosteric regulation model”. This model has been printed successfully using these parameters on Shapeways’ laser sintering printer in the following material: Processed Versatile Plastic (Strong & Flexible Plastic).

Conformational Dynamics Of Biomolecules By Trapped Ion Mobility Spectrometry Dynamics, Juan Camilo Molano-Arévalo

FIU Electronic Theses and Dissertations

One of the main goals in structural biology is to understand the folding mechanisms and three-dimensional structure of biomolecules. Many biomolecular systems adopt multiple structures as a function of their microenvironment, which makes them difficult to be characterized by traditional structural biology tools (e.g., NMR, X-ray crystallography). As an alternative, complementary tools that can capture and sample multiple conformations needed to be developed. In the present work, we pioneered the application of a new variant of ion mobility spectrometry, trapped ion mobility spectrometry (TIMS), which provides high mobility resolving power and the possibility to study kinetically trapped intermediates as a …

Model File Name: 1ehz-Trna(Thick).Stl, Michelle Howell, Karin Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: 1ehz-tRNA(thick).stl

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of Phe-tRNA in a thick stick-representation (PDB: 1ehz), designed to go with a teaching module comparing DNA and RNA basic structures and functions. The printable model is already uploaded to Shapeways.com under the name “tRNA-Phe small”. This model has been printed successfully using these parameters on Shapeways’ laser sintering printer in the following materials: Strong & Flexible Plastic and Elasto Plastic.

Model File Name: 1lmb-Dbd-Tfmono.Stl, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: 1lmb-DBD-TFmono.stl

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of the DNA binding domain of a Lambda repressor transcription factor monomer that accompanies the full color DNA helix (PDB: 1lmb). It is in a cartoon ribbon representation with key amino acid residues in stick representation to highlight interactions with the DNA. This model is designed to accompany a teaching module illustrating transcription factor-DNA binding. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Lambda TF DBD”. This model has been printed …

Model File Name: 1ehz-Trna(Thin-Big).X3d, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: 1ehz-tRNA(thin-big).x3d

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of Phe-tRNA in a large, but thin stick-representation (PDB: 1ehz), designed to go with a teaching module comparing DNA and RNA basic structures and functions. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Full color Phe-tRNA (1ehz)”. This model has been printed successfully using these parameters on Shapeways’ laser sintering printer in the following material: Strong & Flexible Plastic.

Model File Name: 1lmb-Dnalong_Fordimer-Test6b.Stl, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: 1lmb-DNAlong_fordimer-test6b.stl

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of the 19-bp segment of DNA to which Lambda repressor transcription factor interacts (PDB: 1lmb). It is in a stick representation and has been designed with sites to add magnets to illustrate binding interactions with the transcription factor. Sphere magnets with a 1/8” diameter can be purchased separately from K&J Magnets. The model can interact with the dimer form of the transcription factor. This model is designed to accompany a teaching module illustrating transcription factor-DNA binding. The printable model …

Model File Name: 1lmb-Tfdimer-Mags-Joints-Jnd-Sc1-8-Parts-V4b.Stl, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: 1lmb-TFdimer-mags-joints-jnd-sc1-8-parts-v4b.stl

Additional files: 1lmb-Lys-Ser-extras-v4b.stl and 1lmb-TFdimer-Leu-v4b.stl

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of a ribbon and stick representation of the transcription factor lambda repressor (PDB: 1lmb). Key amino acid residues are in stick representation to illustrate the interactions between the repressor and the DNA to which it binds. Some of these residues have been designed with sites to add magnets to illustrate these interactions. Sphere magnets with a 1/8” diameter can be purchased separately from K&J Magnets. Some of the residues can be interchanged with other …

Model File Name: Dna-294bp-Magnet-Supercoil.Stl, Michelle Howell, Karin V. Van Dijk, Kalika Mahato, Rebecca Roston

3-D Printed Model Structural Files

Model file name: DNA-294bp-magnet-supercoil.stl

Authors: Michelle E Howell, Karin van Dijk, Kalika Mahato, Rebecca L Roston

This is a teaching model of a long, thin representation of double stranded DNA (294 bp). The DNA model has small sites on the ends where the user can glue magnets to mimic circular DNA, and to aid in manipulating the model. Disc magnets with a diameter of 1/8” or 1/10” and thickness of 1/16” can be purchased online from K&J Magnetics and glued into the magnet sites. The model is designed to go with a teaching module on DNA supercoiling. The model can …

Model File Name: Dna-294bp-Handle-Supercoil.Stl, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: DNA-294bp-handle-supercoil.stl

Authors: Michelle E Howell, Karin van Dijk, Kalika Mahato, Rebecca L Roston

This is a teaching model of a long, thin representation of double stranded DNA (294 bp). The DNA model has small handles on the ends to aid in holding and manipulating the model. The model is designed to go with a teaching module on DNA supercoiling. The model can be accompanied by Nucleosome and H1 histone models to demonstrate DNA packaging in the cell. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “294bp DNA (handles)”. …

Model File Name: Dna-420bp-Handle-Supercoil.Stl, Michelle Howell, Karin V. Van Dijk, Kalika Mahato, Rebecca Roston

3-D Printed Model Structural Files

Model file name: DNA-420bp-handle-supercoil.stl

Authors: Michelle E Howell, Karin van Dijk, Kalika Mahato, Rebecca L Roston

This is a teaching model of a long, thin representation of double stranded DNA (420 bp). The DNA model has small handles on the ends to aid in holding and manipulating the model. The model is designed to go with a teaching module on DNA supercoiling. The model can be accompanied by Nucleosome and H1 histone models to demonstrate DNA packaging in the cell. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “420bp DNA (handles)”. …

Model File Name: Dnalong-3pc-Lego.Stl, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: DNAlong-3pc-Lego.stl

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of a stick representation of the DNA to which the transcription factor lambda repressor binds (PDB: 1lmb). This model can be adapted to accompany a teaching module illustrating transcription factor-DNA binding. The model has been designed in 3 parts that can be joined together by Lego®-style junctions. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Lego DNA with GCbp”. This model has been printed successfully using these parameters on Shapeways’ laser …

Model File Name: Dna-420bp-Magnet-Supercoil.Stl, Michelle Howell, Karin V. Van Dijk, Kalika Mahato, Rebecca Roston

3-D Printed Model Structural Files

Model file name: DNA-420bp-magnet-supercoil.stl

Authors: Michelle E Howell, Karin van Dijk, Kalika Mahato, Rebecca L Roston

This is a teaching model of a long, thin representation of double stranded DNA (420 bp). The DNA model has small sites on the ends where the user can glue magnets to mimic circular DNA, and to aid in manipulating the model. Disc magnets with a diameter of 1/8” or 1/10” and thickness of 1/16” can be purchased online from K&J Magnetics and glued into the magnet sites. The model is designed to go with a teaching module on DNA supercoiling. The model can …

Model File Name: H1-Protein.Stl, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: H1-protein.stl

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of a crude representation of an H1-protein intended to accompany the nucleosome and a long, thin double stranded DNA helix model in order to illustrate DNA packaging and supercoiling. This model is designed to go with a teaching module on DNA supercoiling. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Histone H1 protein”. This model has been printed successfully using these parameters on Shapeways’ laser sintering printer in the following materials: Strong …

Model File Name: Dna-Short-Helix.X3d, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: DNA-short-helix.x3d

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of a DNA helix in which the atoms are colored by heteroatom (PDB: 1lmb). This model is designed to go with a teaching module comparing DNA and RNA basic structures and functions, and with one that studies transcription factor-DNA binding. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “DNA helix - polynucleotide molecule”. This model has been printed successfully using these parameters on Shapeways’ binder jetting printer in the Coated Full …

Model File Name: Ssdna.Stl, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: ssDNA.stl

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of a single stranded piece of DNA in stick representation (PDB: 1ehz). This model is designed to go with a teaching module comparing DNA and RNA basic structures and functions. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “ssDNA”. This model has been printed successfully using these parameters on Shapeways’ laser sintering printer in the Elasto Plastic material.

Model File Name: Nucleosome.Stl, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: Nucleosome.stl

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of a crude representation of a nucleosome intended to accompany the H1 histone protein and a long, thin double stranded DNA helix model in order to illustrate DNA packaging and supercoiling. This model is designed to go with a teaching module on DNA supercoiling. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Nucleosome”. This model has been printed successfully using these parameters on Shapeways’ laser sintering printer in the Strong & Flexible …

Model File Name: Tf-Monomer-Stick.Stl, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: TF-monomer-stick.stl

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of a ribbon and stick representation of a Lambda repressor transcription factor monomer that accompanies the full color DNA helix (PDB: 1lmb). This model is designed to go with a teaching module illustrating transcription factor-DNA binding. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Lambda TF monomer”. This model has been printed successfully using these parameters on Shapeways’ laser sintering printer in the Strong & Flexible Plastic material.