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Articles 1 - 19 of 19
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Rational Design Of Peptide-Based Materials Informed By Multiscale Molecular Dynamics Simulations, Dhwanit Rahul Dave
Rational Design Of Peptide-Based Materials Informed By Multiscale Molecular Dynamics Simulations, Dhwanit Rahul Dave
Dissertations, Theses, and Capstone Projects
The challenge of establishing a sustainable and circular economy for materials in medicine and technology necessitates bioinspired design. Nature's intricate machinery, forged through evolution, relies on a finite set of biomolecular building blocks with through-bond and through-space interactions. Repurposing these molecular building blocks requires a seamless integration of computational modeling, design, and experimental validation. The tools and concepts developed in this thesis pioneer new directions in peptide-materials design, grounded in fundamental principles of physical chemistry. We present a synergistic approach that integrates experimental designs and computational methods, specifically molecular dynamics simulations, to gain in-depth molecular insights crucial for advancing the …
Exogenous Factors That Impact Huntingtin Aggregation, Adam Skeens
Exogenous Factors That Impact Huntingtin Aggregation, Adam Skeens
Graduate Theses, Dissertations, and Problem Reports
While expansion of a polyglutamine (polyQ) domain is the immediate cause of huntingtin (htt) aggregation associated with Huntington’s Disease (HD), other cellular factors modify aggregation. These include interactions with cellular membranes, protein biding partners, molecular crowding, and proteinaceous seeds. Here, two important factors are biophysically characterized: 1) the interaction of htt with endomembranes and 2) proteinaceous seeds obtained from a variety of htt-derived peptides. In the first project, the aggregation of htt at bilayer interfaces and in the presence of divalent cations was investigated. A major cellular factor implicated in altered htt aggregation is the binding of lipids. Furthermore, the …
Biophysical Insights Into Peptide And Alcohol Perturbations On Biomimetic Membranes, Michael Hai Nguen
Biophysical Insights Into Peptide And Alcohol Perturbations On Biomimetic Membranes, Michael Hai Nguen
Electronic Theses and Dissertations
Biological membranes exist in every domain of life. Life exists due to the presence of these special structures for which we take for granted. They are composed of fatty lipids and workhorse proteins and act as the premier interface of biological processes. Due to the sheer quantity and complexity within their thin boundary, studying their actions and properties pose challenges to researchers. As a result, simplified biomembrane mimics are employed regularly. We will use several types of biomembrane mimics to understand fundamental properties of membranes. In the present thesis, we also attempt to move beyond the canonical structure-based theories upon …
Using Molecular Dynamics Simulations To Decipher Mechanistic Details Of Biomolecular Processes Of Biology And Biotechnology Oriented Applications, Adithya Polasa
Graduate Theses and Dissertations
Researchers in chemistry and biology often utilize computer simulations, in conjunction with experimental data, to model and predict the structures, energies, kinetics, processes, and functions of the systems that are their focus of study, ranging from single molecules to whole viruses. Here, we use molecular dynamics (MD) techniques to gain a deeper understanding of biomolecular processes in biology and biotechnology-oriented applications. Using a mixture of equilibrium and non-equilibrium MD simulations, this work describes the insertion process of YidC at the atomic level. In order to better comprehend the insertion process, several docking models of YidC-Pf3 in the lipid bilayer were …
Biomimetic Synthesis Of Palladium Nanoparticles For Catalytic Application, Emily A. Groover
Biomimetic Synthesis Of Palladium Nanoparticles For Catalytic Application, Emily A. Groover
Electronic Theses and Dissertations
The synthesis of palladium nanoparticles (Pd NPs) using materials-directed peptides is a novel, nontoxic approach which exerts a high level of control over the particle size and shape. This biomimetic technique is environmentally benign, featuring nonhazardous ligands and ambient conditions. Nanoparticles are extremely reactive catalysts, boasting a large surface-to-volume ratio when compared to their bulk counterparts. The rational design of these nanoparticles using peptides has been very successful in aqueous environments, but no research has been done to apply it in organic systems. As such, the biomimetic synthesis of Pd NPs in an organic system is here investigated, with ethanol …
Exploration Of Fluorinated Α,Β-Dehydroamino Acids And Their Structure, Austin Lesueur
Exploration Of Fluorinated Α,Β-Dehydroamino Acids And Their Structure, Austin Lesueur
Undergraduate Honors Theses
This thesis explores the synthesis of fluorinated α,β-dehydroamino acids, specifically a fluorinated dehydrovaline derivative. Previous work has been done on the equivalent dehydrovaline derivative without fluorine present and this work builds toward the fluorinated version with the goal of comparing the two structurally. The synthesis presented here pulls from previous synthetic strategies employed for dehydrovaline while also exploring the synthetic impact of the electronegative fluorine atoms.
Reeling In New Antibiotics: Synthesis And Antimicrobial Susceptibility Testing Of Zinc-Binding Clavanins From Styela Clava (Sea Squirt), Eduardo Badillo-Colberg
Reeling In New Antibiotics: Synthesis And Antimicrobial Susceptibility Testing Of Zinc-Binding Clavanins From Styela Clava (Sea Squirt), Eduardo Badillo-Colberg
Honors Scholar Theses
Clavanins have been a quite rarely studied antimicrobial peptide (AMP) family. Though the data in the few studies published on the matter and in theoretical experimental data presented by the Wang lab in their peptide library creation [14], in that the members of this family could potentially be quite effective novel antimicrobial candidates. Among those that have been targets of studies, Clavanin A has been at the forefront of this endeavor of finding effective novel antimicrobial peptides[14]. In these aforementioned studies, Clavanin A has been shown to be quite effective against many different bacterial strains, which begs the question as …
Minimalistic Peptide-Based Supramolecular Systems Relevant To The Chemical Origin Of Life, Daniela Kroiss
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 …
Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang
Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang
Dissertations, Theses, and Capstone Projects
Interactions between proteins play a key role in nearly all cellular process, and therefore, disruption of such interactions may lead to many different types of cellular dysfunctions. Hence, pathologic protein-protein interactions (PPIs) constitute highly attractive drug targets and hold great potential for developing novel therapeutic agents for the treatment of incurable human diseases. Unfortunately, the identification of PPI inhibitors is an extremely challenging task, since traditionally used small molecule ligands are mostly unable to cover and anchor on the extensive flat surfaces that define those binary protein complexes. In contrast, large biomolecules such as proteins or peptides are ideal fits …
Genetically Engineered Polypeptides As Biomimetic Light Harvesting Optical Antenna, Jason P. Seeley
Genetically Engineered Polypeptides As Biomimetic Light Harvesting Optical Antenna, Jason P. Seeley
Legacy Theses & Dissertations (2009 - 2024)
Natural resources useful for the generation of energy are limited. The development of efficient materials capable of utilizing the abundant free solar radiation is of considerable interest. Utilization of otherwise wasted energy sources, including solar radiation, is a progressive step in the quest for sustainable energy. Solar radiation incident upon the earth’s surface exceeds current energy requirements and motivates scientists to investigate and develop functional devices and nanomaterials including light harvesting complexes (LHC) capable of capturing solar radiation for energy conversion and storage.
2-D Electrophoresis Modeling Of Multienzyme Cutting Of Polypeptides, Howard Mayes
2-D Electrophoresis Modeling Of Multienzyme Cutting Of Polypeptides, Howard Mayes
Theses
2-Dimensional Electrophoresis is one of the tools in the identification of proteins by molecular weight and pH. The display of molecular weight allows the researcher to quickly identify whether a specific protein or peptide string is in the sample. The pH measurement allows even better resolution between different species in the sample. The MultiEnzyme ElectroPhoresis (MEEP) program tries to model that by providing a graph that displays separated protein strings by both molecular weight and pH. The ability to cleave the protein with 43 different enzyme variations allows the researcher to analyze appropriate enzymes to isolate a protein subsequence before …
Ligand Binding Studies Of A Peptide Targeting Helix 69 Of 23s Rrna In Bacterial Ribosomes, Hyosuk Seo
Ligand Binding Studies Of A Peptide Targeting Helix 69 Of 23s Rrna In Bacterial Ribosomes, Hyosuk Seo
Wayne State University Dissertations
In the development of finding a peptide targeting H69 of 23S rRNA in bacterial ribosomes, phage display was employed at pH 5.5, a buffer condition previously reported of H69 preferring a closed conformation. After sequencing, several peptides were chosen through sequence alignment, followed by preparation using solid-phase peptide synthesis. The peptides were characterized using MALDI-TOF and purified with HPLC. A truncated peptide TARHIY was selected from FID assay. Through binding studies using ESI-MS, SPR, BLItz, and NMR, the binding properties of the peptide to H69 were determined, such as binding affinity, stoichiometry, and interaction site. The peptide exhibited moderate binding …
Inhibition Of Apobec3g Activity Impedes Double-Stranded Dna Repair, Ponnandy Prabhu, Shivender Shandilya, Elena Britan-Rosich, Adi Nagler, Celia Schiffer, Moshe Kotler
Inhibition Of Apobec3g Activity Impedes Double-Stranded Dna Repair, Ponnandy Prabhu, Shivender Shandilya, Elena Britan-Rosich, Adi Nagler, Celia Schiffer, Moshe Kotler
Celia A. Schiffer
The cellular cytidine deaminase APOBEC3G (A3G) was first described as an anti-HIV-1 restriction factor, acting by directly deaminating reverse transcripts of the viral genome. HIV-1 Vif neutralizes the activity of A3G, primarily by mediating degradation of A3G to establish effective infection in host target cells. Lymphoma cells, which express high amounts of A3G, can restrict Vif-deficient HIV-1. Interestingly, these cells are more stable in the face of treatments that result in double-stranded DNA damage, such as ionizing radiation and chemotherapies. Previously, we showed that the Vif-derived peptide (Vif25-39) efficiently inhibits A3G deamination, and increases the sensitivity of lymphoma cells to …
Designing Fret Assays To Study Electrostatic Interactions Pertaining To The Binding Of Intrinsically Disordered Proteins, Ashley Ann Howard
Designing Fret Assays To Study Electrostatic Interactions Pertaining To The Binding Of Intrinsically Disordered Proteins, Ashley Ann Howard
Graduate Theses and Dissertations
Fibroblast growth factor receptor plays a major role in several biological processes. Without FGFR, a human cannot live. FGFR is involved in cell differentiation and wound healing. Of course, if FGFR signaling becomes unregulated, it causes severe distress in the body. Several cancers are contributed to high signaling levels, as well as developmental conditions like rickets and Kallmann’s syndrome. FGFR is thought to undergo an auto-inhibition (or self-regulatory) process in order to try to facilitate regulation. The exact method of this inhibition is currently unknown, but is proposed to involve the unstructured acid box region of FGFR. We developed a …
Achieving High Accuracy Prediction Of Minimotifs, Tian Mi, Sanguthevar Rajasekaran, Jerlin Camilus Merlin, Michael R. Gryk, Martin Schiller
Achieving High Accuracy Prediction Of Minimotifs, Tian Mi, Sanguthevar Rajasekaran, Jerlin Camilus Merlin, Michael R. Gryk, Martin Schiller
Life Sciences Faculty Research
The low complexity of minimotif patterns results in a high false-positive prediction rate, hampering protein function prediction. A multi-filter algorithm, trained and tested on a linear regression model, support vector machine model, and neural network model, using a large dataset of verified minimotifs, vastly improves minimotif prediction accuracy while generating few false positives. An optimal threshold for the best accuracy reaches an overall accuracy above 90%, while a stringent threshold for the best specificity generates less than 1% false positives or even no false positives and still produces more than 90% true positives for the linear regression and neural network …
Novel Cinchona Alkoloid Derived Ammonium Salts As Phase-Transfer Catalysts For The Asymmetric Synthesis Of Beta-Hydroxy Alpha-Amino Acids Via Aldol Reactions And Total Synthesis Of Celogentin C., Bing Ma
Theses and Dissertations
Project I. Cinchona alkaloid-derived quaternary ammonium salts have been successfully used as phase-transfer catalysts, particularly in asymmetric alkylations. Our group applied this type of catalyst in the synthesis of β-hydroxy α-amino acids via aldol reactions and discovered that the Park-Jew catalyst afforded good yields and good enantiomeric excess of the syn diasteromers, but negligible diastereoselectivity. This project was therefore focused on the synthesis of novel cinchonidine-derived catalysts with the Park-Jew catalyst as the lead structure. The C3 position of cinchonidine nucleus was modified to achieve dimers and catalysts possessing electron-deficient alkyne and alkene moieties. Synthesized catalysts were tested in the …
Development Of Polymer Monoliths For The Analysis Of Peptides And Proteins, Binghe Gu
Development Of Polymer Monoliths For The Analysis Of Peptides And Proteins, Binghe Gu
Theses and Dissertations
Several novel polymer monoliths for the analysis of peptides and proteins were synthesized using polyethylene glycol diacrylate (PEGDA) as crosslinker. Photo-initiated copolymerization of polyethylene glycol methyl ether acrylate and PEGDA yielded an inert monolith that could be used for size exclusion liquid chromatography of peptides and proteins. This macroscopically uniform monolith did not shrink or swell in either water or tetrahydrofuran. More importantly, it was found to resist adsorption of both acidic and basic proteins in aqueous buffer without any organic solvent additives. A strong cation-exchange polymer monolith was synthesized by copolymerization of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and PEGDA. A ternary …
Polymer Microchips For Capillary Electrophoresis And Electric Field Gradient Focusing Of Biomolecules, Ryan Thomas Kelly
Polymer Microchips For Capillary Electrophoresis And Electric Field Gradient Focusing Of Biomolecules, Ryan Thomas Kelly
Theses and Dissertations
Polymeric materials have seen increasing use as microfluidic device substrates due to their low cost and the simplicity of templated fabrication procedures. I showed that poly(methyl methacrylate) (PMMA) microdevices could be enclosed in a boiling water bath, which allowed the seal to form more quickly than in conventional approaches, and enabled microchannels to remain hydrated throughout the bonding process. Microchip capillary electrophoresis (µ-CE) devices were fabricated using water-based enclosure, and a mixture of fluorescently labeled amino acids was separated in 30 s in these microchips. To create more robust capillary electrophoresis (CE) microdevices with improved separation performance, phase-changing sacrificial materials …
The Carboxyl Terminus Of The Bacteriophage T4 Dna Polymerase Is Required For Holoenzyme Complex Formation, Anthony J. Berdis, Patrice Soumillion, Stephen J. Benkovic
The Carboxyl Terminus Of The Bacteriophage T4 Dna Polymerase Is Required For Holoenzyme Complex Formation, Anthony J. Berdis, Patrice Soumillion, Stephen J. Benkovic
Chemistry Faculty Publications
To further elucidate the mechanism and dynamics of bacteriophage T4 holoenzyme formation, a mutant polymerase in which the last six carboxyl-terminal amino acids are deleted, was constructed, overexpressed, and purified to homogeneity. The mutant polymerase, designated ΔC6 exo−, is identical to wild-type exo− polymerase with respect to kcat, kpol, and dissociation constants for nucleotide and DNA substrate. However, unlike wild-type exo− polymerase, the ΔC6 exo− polymerase is unable to interact with the 45 protein to form the stable holoenzyme. A synthetic polypeptide corresponding to the carboxyl terminus of the wild-type exo− polymerase was tested as an in vitro inhibitor of …