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Full-Text Articles in Structural Biology

Decoding The Allosteric Grammar Of Protein Kinases: A Dual-Stream Framework Integrating Protein Language Models And Energy Landscape Frustration Analysis, Will Gatlin, Max Ludwick, Lucas Turano, Brandon Foley, Kamila Riedlova, Vít Škrhák, Marian Novotný, David Hoksza, Gennady M. Verkhivker Jul 2026

Decoding The Allosteric Grammar Of Protein Kinases: A Dual-Stream Framework Integrating Protein Language Models And Energy Landscape Frustration Analysis, Will Gatlin, Max Ludwick, Lucas Turano, Brandon Foley, Kamila Riedlova, Vít Škrhák, Marian Novotný, David Hoksza, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The spatial and energetic encoding of allosteric regulatory sites remains a major challenge in structural biology, frequently representing a “blind spot” for sequence-based artificial intelligence (AI) models. We present a protein language model (PLM)-guided approach complemented by the energy landscape frustration analysis as a dual-stream framework to investigate the relationship between AI prediction of binding sites and biophysical organization of regulatory pockets across the human kinome. By probing a fine-tuned residue-level PLM classifier across 453 kinase structures, a clear performance gap is discovered between highly predictable orthosteric pockets (Types I, I.5, and II) and poorly resolved distal allosteric sites (Type …


Structure-Based Discovery Of Malate Dehydrogenase Inhibitors With Efficacy Against C. Parvum Oocysts, Ankita Bharatbhai Kheni Jun 2026

Structure-Based Discovery Of Malate Dehydrogenase Inhibitors With Efficacy Against C. Parvum Oocysts, Ankita Bharatbhai Kheni

Biochemistry and Molecular Biology

Cryptosporidium parvum, the etiological agent of Cryptosporidiosis (diarrheal illness) represents a significant global health burden, particularly affecting immunodeficient and pediatric populations. Since the parasite has a highly reduced mitochondrion and relies on glycolysis, enzymes such as C. parvum malate dehydrogenase (CpMDH), which are believed to be indispensable for parasite viability due to their pivotal roles in NAD⁺ regeneration and redox balance, remain largely unexplored as therapeutic targets. The present study employed a multifaceted experimental and computational strategy to evaluate the inhibitory activity of two lead-like and drug-like small molecules, referred to as compound 1.8 and compound 1.5, against the cofactor …


Dapagliflozin Attenuates Cisplatin-Induced Nephrotoxicity In Rats Through Modulation Of Ros/Nf-Κb, Bcl2/Bax And Pink1/Parkin Signaling Pathways, Esraa K. Khallaf, Eman A. Ramadan, Mohey M. Elmazar, Marwa M. Safar Jan 2026

Dapagliflozin Attenuates Cisplatin-Induced Nephrotoxicity In Rats Through Modulation Of Ros/Nf-Κb, Bcl2/Bax And Pink1/Parkin Signaling Pathways, Esraa K. Khallaf, Eman A. Ramadan, Mohey M. Elmazar, Marwa M. Safar

Pharmacy

Dapagliflozin (DPG), an anti-diabetic drug, has gained attention for its renal protective effects through multiple molecular pathways, yet its impact on mitophagy in cisplatin (CIS) nephrotoxicity remains unclear. This study aimed to examine the impact of DPG against CIS-induced nephrotoxicity in rats, targeting mainly PINK1/Parkin-mediated mitophagy and inflammatory/apoptotic pathways. Male Sprague Dawley rats received DPG (10 mg/kg; p.o) daily for 14 consecutive days and AKI was induced by a single injection of CIS (7 mg/kg; i.p) on day 10. Blood glucose, serum levels of creatinine and urea nitrogen, oxidative stress, inflammatory, apoptotic, mitophagy markers, and histological changes were assessed. DPG …


Potential Environmental Triggers Of Goodpasture's Disease And The Role Of The Sulfimine Crosslink, Colton S. Miller, Andrea Florian, Elena Pokidysheva Jan 2026

Potential Environmental Triggers Of Goodpasture's Disease And The Role Of The Sulfimine Crosslink, Colton S. Miller, Andrea Florian, Elena Pokidysheva

SPARK Symposium Presentations

Goodpasture’s syndrome (GP) is an autoimmune disorder that primarily affects kidneys and lungs. The main issue for patients with Goodpasture's syndrome is the binding of autoantibodies to the glomerular basement membrane (GBM), which hinders the filtration of blood. A key characteristic of Goodpasture's syndrome is the presence of autoantibodies that target the NC1 domain of the α345 isoform of type IV collagen, a crucial component of the GBM that provides structural support and is critical for filtration function. Sulfilimine bonds crosslink the collagen IV NC1 hexamers, contributing to the stabilization of these structures. A recent clinical case of recurring Goodpasture's …


Development Of A Cure In Principles Of Cell And Molecular Biology, Heather Seitz Aug 2025

Development Of A Cure In Principles Of Cell And Molecular Biology, Heather Seitz

Sabbatical Projects

This project presentation highlights the work done during sabbatical to develop an authentic research experience into BIOL135 Principles of Cell and Molecular Biology. The sabbatical allowed for development time but further work was done to measure impact and outcomes for future implementation.


Characterization Of Sars-Cov-2 Replication And Transcription Complexes Via Structural And Evolutionary Approaches, Amelie Ghirardo, Ben Shabatian, Avishai Aghelian, Kyle Tau, Eleonora Gianti May 2025

Characterization Of Sars-Cov-2 Replication And Transcription Complexes Via Structural And Evolutionary Approaches, Amelie Ghirardo, Ben Shabatian, Avishai Aghelian, Kyle Tau, Eleonora Gianti

Undergraduate Research

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused around 700M cases and over 7M COVID-19-related deaths recorded worldwide (World Health Organization, March 2025). Aiming to effectively combat this and other disease-causing Coronaviruses (CoV), unprecedented research efforts led to the development of new vaccines and antiviral therapies. Due to emergence of variants of concern (VOCs) with increased transmissibility, immune evasion from vaccination, and potential to resist the available treatments, SARS-CoV-2 continues to represent a major threat to global health. Hence, there is a pressing need to discover new antivirals with broad-spectrum efficacy against multiple SARS-CoV-2 variants and related CoVs. This project …


3d Printing Protein-Rrna Mutations In The Ribosome, Abigail Wilson May 2025

3d Printing Protein-Rrna Mutations In The Ribosome, Abigail Wilson

Senior Honors Projects

Sometimes conveying research can be difficult through two-dimension models. In my project, I aimed to highlight the significance of three-dimensional visualization in science, thereby enhancing the understanding of complex biomedical concepts. Through my work in Dr. Steven Gregory’s lab, I have been studying the ribosome – the macromolecular machine that utilizes messenger RNA and transfer RNA to link together amino acids thereby synthesizing proteins. Proteins are critical for most processes that occur within every cell. I specifically focus on the interactions between ribosomal proteins and ribosomal RNA (rRNA) at the peptidyl transferase center – the active site where amino acids …


Induced Mutagenesis In West Nile Virus Non-Structural Protein 3 With A Discussion Of The Mutation's Effects On Viral Properties, Caden Connealy Mar 2025

Induced Mutagenesis In West Nile Virus Non-Structural Protein 3 With A Discussion Of The Mutation's Effects On Viral Properties, Caden Connealy

Honors Program: Senior Projects (Public)

West Nile Virus (WNV), a member of the Flaviviridae family and introduced to the Western hemisphere in 1999, presents a unique and emerging threat to human health. Infection in humans is often mild but can occasionally result in severe neurological impairment and even death. West Nile Virus non-structural protein 3 (NS3) plays an important role in the process of viral genome amplification. More specifically, the C-terminal domain of the protein folds into a helicase enzyme, which is responsible for the “unwinding” of double-stranded RNA intermediates and RNA secondary structure on the WNV genome. This is a vitally important step in …


Fast 3d Printing Of Fine, Continuous, And Soft Fibers Via Embedded Solvent Exchange, Wonsik Eom, Mohammad Tanver Hossain, Vidush Parasramka, Jeongmin Kim, Ryan W. Y. Siu, Kate A. Sanders, Dakota Piorkowski, Andrew Lowe, Hyun Gi Koh, Michael F. L. De Volder, Douglas S. Fudge, Randy H. Ewoldt, Sameh H. Tawfick Jan 2025

Fast 3d Printing Of Fine, Continuous, And Soft Fibers Via Embedded Solvent Exchange, Wonsik Eom, Mohammad Tanver Hossain, Vidush Parasramka, Jeongmin Kim, Ryan W. Y. Siu, Kate A. Sanders, Dakota Piorkowski, Andrew Lowe, Hyun Gi Koh, Michael F. L. De Volder, Douglas S. Fudge, Randy H. Ewoldt, Sameh H. Tawfick

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nature uses fibrous structures for sensing and structural functions as observed in hairs, whiskers, stereocilia, spider silks, and hagfish slime thread skeins. Here, we demonstrate multi-nozzle printing of 3D hair arrays having freeform trajectories at a very high rate, with fiber diameters as fine as 1.5 µm, continuous lengths reaching tens of centimeters, and a wide range of materials with elastic moduli from 5 MPa to 3500 MPa. This is achieved via 3D printing by rapid solvent exchange in high yield stress micro granular gel, leading to radial solidification of the extruded polymer filament at a rate of 2.33 μm/s. …


Phagolysosomes Break Down The Membrane Of A Non-Apoptotic Corpse Independent Of Macroautophagy, Shruti Kolli, Cassidy J. Kline, Kimya M. Rad, Ann M. Wehman Nov 2024

Phagolysosomes Break Down The Membrane Of A Non-Apoptotic Corpse Independent Of Macroautophagy, Shruti Kolli, Cassidy J. Kline, Kimya M. Rad, Ann M. Wehman

Biological Sciences: Faculty Scholarship

Cell corpses must be cleared in an efficient manner to maintain tissue homeostasis and regulate immune responses. Ubiquitin-like Atg8/LC3 family proteins promote the degradation of membranes and internal cargo during both macroautophagy and corpse clearance, raising the question how macroautophagy contributes to corpse clearance. Studying the clearance of non-apoptotic dying polar bodies in Caenorhabditis elegans embryos, we show that the LC3 ortholog LGG-2 is enriched inside the polar body phagolysosome independent of autophagosome formation. We demonstrate that ATG-16.1 and ATG-16.2, which promote membrane association of lipidated Atg8/LC3 proteins, redundantly promote polar body membrane breakdown in phagolysosomes independent of their role …


Impact Of Chytrid Fungal Infection On Muscle Structure In Amphibians, Esther Hassan, Chisom Ukachukwu Nov 2024

Impact Of Chytrid Fungal Infection On Muscle Structure In Amphibians, Esther Hassan, Chisom Ukachukwu

Science University Research Symposium (SURS)

Many fungal infections affect a wide variety of ecosystems. They cause numerous negative consequences, one in particular being the disruption of biodiversity. disrupting biodiversity and leading to numerous negative consequences. A previous study in the Kinsey lab focused on a chytrid fungal disease, Batrachochytrium dendrobatidis (Bd), a species of chytrid fungus. This disease poses a major threat to amphibian populations worldwide. The Bd zoospores infect the epidermis impacting essential systems. This leads to electrolyte transport that is conducted through the epidermis from the environment has now become disrupted and the ions required for daily functions are diminished. Eventually, these lack …


"Deep Learning For Microscope Image Denoising", Nasreen Buhn, Sriya Adunur, Guy Hagen, Jonathan Ventura Oct 2024

"Deep Learning For Microscope Image Denoising", Nasreen Buhn, Sriya Adunur, Guy Hagen, Jonathan Ventura

College of Engineering Summer Undergraduate Research Program

In order to avoid damaging live cells, optical microscope imaging must be conducted under low-excitation light intensity and/or short exposure times, resulting in low signal-to-noise ratios (SNR). Deep learning methods offer an effective solution for removing microscope noise, utilizing algorithms that are able to reconstruct finer features in low SNR images. This research explores the denoising capability of several deep learning methods based on PSNR and SSIM. Tested methods include traditional approaches (BMED), supervised learning (CARE and Restormer), and unsupervised methods (Noise2Fast, N2V, SSD-Unsupervised, and SASSID). The Restormer model, which employs an encoder-decoder transformer architecture and progressive learning, stood out …


Cryo-Em Reconstruction Of Oleate Hydratase Bound To A Phospholipid Membrane Bilayer, Michael L. Oldham, M. Zuhaib Qayyum, Ravi C. Kalathur, Charles O. Rock, Christopher D. Radka Aug 2024

Cryo-Em Reconstruction Of Oleate Hydratase Bound To A Phospholipid Membrane Bilayer, Michael L. Oldham, M. Zuhaib Qayyum, Ravi C. Kalathur, Charles O. Rock, Christopher D. Radka

Markey Cancer Center Faculty Publications

Oleate hydratase (OhyA) is a bacterial peripheral membrane protein that catalyzes FAD-dependent water addition to membrane bilayer-embedded unsaturated fatty acids. The opportunistic pathogen Staphylococcus aureus uses OhyA to counteract the innate immune system and support colonization. Many Gram-positive and Gram-negative bacteria in the microbiome also encode OhyA. OhyA is a dimeric flavoenzyme whose carboxy terminus is identified as the membrane binding domain; however, understanding how OhyA binds to cellular membranes is not complete until the membrane-bound structure has been elucidated. All available OhyA structures depict the solution state of the protein outside its functional environment. Here, we employ liposomes to …


Structural Analysis Of Dj-1 Glyoxalase Activity By Mix-And-Inject Serial Synchrotron Crystallography, Coleman Dolamore Jul 2024

Structural Analysis Of Dj-1 Glyoxalase Activity By Mix-And-Inject Serial Synchrotron Crystallography, Coleman Dolamore

Department of Biochemistry: Dissertations, Theses, and Student Research

Observing enzyme structures while they are catalyzing a reaction has been a major goal of both enzymology and structural biology for decades. With the advent of time-resolved serial X-ray crystallography using X-ray free electron lasers (XFELs) and synchrotron sources, enzyme reactions can be monitored in real time in crystallo. Here, we use two different approaches to study related enzymes involved in methylglyoxal detoxification. For human DJ-1, we used pink beam mix-and-inject serial crystallography (MISC) at the Advanced Photon Source (BioCARS 14-ID) to probe the controversial mechanism of DJ-1’s action on methylglyoxal by using serial Laue diffraction. The high flux …


A Structural Role For Tryptophan In Proteins, And The Ubiquitous Trp CΔ1—H&Centerdot;&Centerdot;&Centerdot;O=C (Backbone) Hydrogen Bond, Michal Szczygiel, Urszula Derewenda, Steve Scheiner, Wladek Minor, Zygmunt S. Derewenda Jun 2024

A Structural Role For Tryptophan In Proteins, And The Ubiquitous Trp CΔ1—H&Centerdot;&Centerdot;&Centerdot;O=C (Backbone) Hydrogen Bond, Michal Szczygiel, Urszula Derewenda, Steve Scheiner, Wladek Minor, Zygmunt S. Derewenda

Chemistry and Biochemistry Faculty Publications

Tryptophan is the most prominent amino acid found in proteins, with multiple functional roles. Its side chain is made up of the hydrophobic indole moiety, with two groups that act as donors in hydrogen bonds: the Nε—H group, which is a potent donor in canonical hydrogen bonds, and a polarized Cδ1—H group, which is capable of forming weaker, noncanonical bonds. Due to adjacent electron-withdrawing moieties, C—H···O hydrogen bonds are ubiquitous in macromolecules, albeit contingent on the polarization of the donor C—H group. Consequently, Cα groups (adjacent to the carbonyl and amino groups of flanking peptide …


Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova Jan 2024

Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of …


Cyp6g2 Is The Major P450 Epoxidase Responsible For Juvenile Hormone Biosynthesis In Drosophila Melanogaster, Qiangqiang Jia, Liu Yang, Jiamin Wen, Suning Liu, Di Wen, Wei Luo, Weihua Wang, Subba R. Palli, Li Sheng Jan 2024

Cyp6g2 Is The Major P450 Epoxidase Responsible For Juvenile Hormone Biosynthesis In Drosophila Melanogaster, Qiangqiang Jia, Liu Yang, Jiamin Wen, Suning Liu, Di Wen, Wei Luo, Weihua Wang, Subba R. Palli, Li Sheng

Entomology Faculty Publications

Background Juvenile hormones (JH) play crucial role in regulating development and reproduction in insects. The most common form of JH is JH III, derived from MF through epoxidation by CYP15 enzymes. However, in the higher dipterans, such as the fruitfly, Drosophila melanogaster, a bis-epoxide form of JHB3, accounted most of the JH detected. Moreover, these higher dipterans have lost the CYP15 gene from their genomes. As a result, the identity of the P450 epoxidase in the JH biosynthesis pathway in higher dipterans remains unknown.

Results In this study, we show that Cyp6g2 serves as the major JH epoxidase responsible for …


The Mechanoreceptor Piezo Is Required For Spermatogenesis In Bombyx Mori, Zhongjie Zhang, Xiaojing Liu, Bo Hu, Kai Chen, Ye Yu, Chenxin Sun, Dalin Zhu, Hua Bai, Subba Reddy Palli, Anjiang Tan Jan 2024

The Mechanoreceptor Piezo Is Required For Spermatogenesis In Bombyx Mori, Zhongjie Zhang, Xiaojing Liu, Bo Hu, Kai Chen, Ye Yu, Chenxin Sun, Dalin Zhu, Hua Bai, Subba Reddy Palli, Anjiang Tan

Entomology Faculty Publications

Background The animal sperm shows high diversity in morphology, components, and motility. In the lepidopteran model insect, the silkworm Bombyx mori, two types of sperm, including nucleate fertile eupyrene sperm and anucleate unfertile apyrene sperm, are generated. Apyrene sperm assists fertilization by facilitating the migration of eupyrene spermatozoa from the bursa copulatrix to the spermatheca. During spermatogenesis, eupyrene sperm bundles extrude the cytoplasm by peristaltic squeezing, while the nuclei of the apyrene sperm bundles are discarded with the same process, forming matured sperm.

Results In this study, we describe that a mechanoreceptor BmPiezo, the sole Piezo ortholog in B. mori, …


A Guide To Otoliths Of Minnesota Fishes, Baylor J. Short Jan 2024

A Guide To Otoliths Of Minnesota Fishes, Baylor J. Short

Journal of Earth and Life Science

Investigations into the diet patterns of piscivores can provide crucial information on predator-prey relationships, population dynamics, and responses to changing ecosystems. However, digestive processes often remove or alter physical characteristics that are traditionally used to identify consumed fish. This problem has been addressed to some degree with advances in molecular technologies, although these methods can be costly and require specific training and equipment to do so. In contrast, bony structures such as otoliths, vertebrae, cleithra, and others frequently have morphologies that are unique among families, genera, and species. Because these structures are resistant to digestion, they can be used to …


Inactive Metallopeptidase Homologs: The Secret Lives Of Pseudopeptidases, Peter Lyons Jan 2024

Inactive Metallopeptidase Homologs: The Secret Lives Of Pseudopeptidases, Peter Lyons

Faculty Publications

Inactive enzyme homologs, or pseudoenzymes, are proteins, found within most enzyme families, that are incapable of performing catalysis. Rather than catalysis, they are involved in protein-protein interactions, sometimes regulating the activity of their active enzyme cousins, or scaffolding protein complexes. Pseudoenzymes found within metallopeptidase families likewise perform these functions. Pseudoenzymes within the M14 carboxypeptidase family interact with collagens within the extracellular space, while pseudopeptidase members of the M12 "a disintegrin and metalloprotease" (ADAM) family either discard their pseudopeptidase domains as unnecessary for their roles in sperm maturation or utilize surface loops to enable assembly of key complexes at neuronal synapses. …


Evaluating The Response Of Glycine Soja Accessions To Fungal Pathogen Macrophomina Phaseolina During Seedling Growth, Shirley Jacquet, Layla Rashad, Sonia Viera, Francisco Reta, Juan Reta Nov 2023

Evaluating The Response Of Glycine Soja Accessions To Fungal Pathogen Macrophomina Phaseolina During Seedling Growth, Shirley Jacquet, Layla Rashad, Sonia Viera, Francisco Reta, Juan Reta

Biological Science Student Working Papers

Charcoal rot caused by the fungal pathogen Macrophomina phaseolina (Tassi) Goid is one of various devastating soybean (Glycine max (L.) Merr.) diseases, which can severely reduce crop yield. The investigation into the genetic potential for charcoal rot resistance of wild soybean (Glycine soja) accessions will enrich our understanding of the impact of soybean domestication on disease resistance; moreover, the identified charcoal rot-resistant lines can be used to improve soybean resistance to charcoal rot. The objective of this study was to evaluate the resistance of wild soybean accessions to M. phaseolina at the seedling stage and thereby select the disease-resistant lines. …


Predicted Structure And Analysis Of The Glycoprotein From Sars-Cov-2 Variants Of Interest, Boris Shabaltiy Oct 2023

Predicted Structure And Analysis Of The Glycoprotein From Sars-Cov-2 Variants Of Interest, Boris Shabaltiy

Honors Program: Senior Projects (Public)

SARS-CoV-2 has had a devastating effect on the world, and while the public concern and severity of the diseased caused by it have decreased, it is still crucial to monitor the virus for mutations so we can rapidly identify new variants of concern, and then rapidly prepare new vaccines and treatments. The SARS-CoV-2 spike (S) protein from the first isolates of the virus (root variant) was structurally characterized in early 2021. The spike protein structure, designated 7CZW, was uploaded to RCSB Protein Data Bank (RCSB PDB). All subsequent mutations the S protein has accumulated are based on the amino acid …


Structural Diversity And Stress Regulation Of The Plant Immunity-Associated Calmodulin-Binding Protein 60 (Cbp60) Family Of Transcription Factors In Solanum Lycopersicum (Tomato), Vanessa Shivnauth, Sonya Pretheepkumar, Eric J. R. Marchetta, Christina A. M. Rossi, Keaun Amani, Christian Castroverde Jul 2023

Structural Diversity And Stress Regulation Of The Plant Immunity-Associated Calmodulin-Binding Protein 60 (Cbp60) Family Of Transcription Factors In Solanum Lycopersicum (Tomato), Vanessa Shivnauth, Sonya Pretheepkumar, Eric J. R. Marchetta, Christina A. M. Rossi, Keaun Amani, Christian Castroverde

Biology Faculty Publications

Cellular signaling generates calcium (Ca2+) ions, which are ubiquitous secondary messengers decoded by calcium-dependent protein kinases, calcineurins, calreticulin, calmodulins (CAMs), and CAM-binding proteins. Previous studies in the model plant Arabidopsis thaliana have shown the critical roles of the CAM-BINDING PROTEIN 60 (CBP60) protein family in plant growth, stress responses, and immunity. Certain CBP60 factors can regulate plant immune responses, like pattern-triggered immunity, effector-triggered immunity, and synthesis of major plant immune-activating metabolites salicylic acid (SA) and N-hydroxypipecolic acid (NHP). Although homologous CBP60 sequences have been identified in the plant kingdom, their function and regulation in most species remain unclear. In …


The Metabolomics Workbench File Status Website: A Metadata Repository Promoting Fair Principles Of Metabolomics Data, Christian D. Powell, Hunter N. B. Moseley Jul 2023

The Metabolomics Workbench File Status Website: A Metadata Repository Promoting Fair Principles Of Metabolomics Data, Christian D. Powell, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

Background: An updated version of the mwtab Python package for programmatic access to the Metabolomics Workbench (MetabolomicsWB) data repository was released at the beginning of 2021. Along with updating the package to match the changes to MetabolomicsWB’s ‘mwTab’ file format specification and enhancing the package’s functionality, the included validation facilities were used to detect and catalog file inconsistencies and errors across all publicly available datasets in MetabolomicsWB.

Results: The MetabolomicsWB File Status website was developed to provide continuous validation of MetabolomicsWB data files and a useful interface to all found inconsistencies and errors. This list of detectable issues/errors include format …


Modeling Accuracy Matters: Aligning Molecular Dynamics With 2d Nmr Derived Noe Restraints, Milan Patel May 2023

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 …


Kegg_Pull: A Software Package For The Restful Access And Pulling From The Kyoto Encyclopedia Of Gene And Genomes, Erik D. Huckvale, Hunter N. B. Moseley Mar 2023

Kegg_Pull: A Software Package For The Restful Access And Pulling From The Kyoto Encyclopedia Of Gene And Genomes, Erik D. Huckvale, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

Background: The Kyoto Encyclopedia of Genes and Genomes (KEGG) provides organized genomic, biomolecular, and metabolic information and knowledge that is reasonably current and highly useful for a wide range of analyses and modeling. KEGG follows the principles of data stewardship to be findable, accessible, interoperable, and reusable (FAIR) by providing RESTful access to their database entries via their web-accessible KEGG API. However, the overall FAIRness of KEGG is often limited by the library and software package support available in a given programming language. While R library support for KEGG is fairly strong, Python library support has been lacking. Moreover, there …


Abstract 1858: Active And Allosteric Site Evolution Directs Ordered Water Use In Kinesin Catalysis, Micquel Downs, David Worthylake, Jessica Richard, Courtney Parke, Elizabeth Kim, Edward J. Wojcik, Sunyoung Kim Mar 2023

Abstract 1858: Active And Allosteric Site Evolution Directs Ordered Water Use In Kinesin Catalysis, Micquel Downs, David Worthylake, Jessica Richard, Courtney Parke, Elizabeth Kim, Edward J. Wojcik, Sunyoung Kim

School of Graduate Studies Faculty Publications

2023 American Society for Biochemistry and Molecular Biology (ASBMB) Annual Meeting; March 25 - 28, 2023; Seattle, WA


Structural Files For The Etr1 Ethylene-Receptor Dimer Based On Computational Modeling, Beenish J. Azhar, Safdar Abbas, Sitwat Aman, Maria V. Yamburenko, Wei Chen, Lena Muller, Buket Uzun, David A. Jewell, Jian Dong, Samina N. Shakeel, Georg Groth, Brad M. Binder, Gevorg Grigoryan, G. Eric Schaller Jan 2023

Structural Files For The Etr1 Ethylene-Receptor Dimer Based On Computational Modeling, Beenish J. Azhar, Safdar Abbas, Sitwat Aman, Maria V. Yamburenko, Wei Chen, Lena Muller, Buket Uzun, David A. Jewell, Jian Dong, Samina N. Shakeel, Georg Groth, Brad M. Binder, Gevorg Grigoryan, G. Eric Schaller

Dartmouth Scholarship

Structural models for the ETR1 homodimer were generated with AlphaFold-Multimer. Coppers were modeled under two potential coordinations involving Cys65 and His69 of the ETR1 homodimer, one in which the two coppers are bound independently and do not share an interaction with each other, and another where they are closely bonded.

See the following publication for details: Azhar, B.J., Abbas, S., Aman, S., Yamburenko, M.V., Chen, W., Müller, L., Uzun, B., Jewell, D.A., Dong, J., Shakeel, S.N., Groth, G., Binder, B.M., Grigoryan, G., Schaller, G.E. (2023) Basis for high-affinity ethylene binding by the ethylene receptor ETR1 of Arabidopsis. Proc. Natl. Acad. …


A Pipeline To Generate Deep Learning Surrogates Of Genome-Scale Metabolic Models, Achilles Rasquinha Nov 2022

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

School of Computing: 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 …


Seqcode: A Nomenclatural Code For Prokaryotes Described From Sequence Data, Brian P. Hedlund, Maria Chuvochina, Philip Hugenholtz, Konstantinos T. Konstantinidis, Alison E. Murray, Marike Palmer, Donovan H. Parks, Alexander J. Probst, Anna-Louise Reysenbach, Luis M. Rodriguez-R, Ramon Rossello-Mora, Iain C. Sutcliffe, Stephanus N. Venter, William B. Whitman Sep 2022

Seqcode: A Nomenclatural Code For Prokaryotes Described From Sequence Data, Brian P. Hedlund, Maria Chuvochina, Philip Hugenholtz, Konstantinos T. Konstantinidis, Alison E. Murray, Marike Palmer, Donovan H. Parks, Alexander J. Probst, Anna-Louise Reysenbach, Luis M. Rodriguez-R, Ramon Rossello-Mora, Iain C. Sutcliffe, Stephanus N. Venter, William B. Whitman

Life Sciences Faculty Research

Most prokaryotes are not available as pure cultures and therefore ineligible for naming under the rules and recommendations of the International Code of Nomenclature of Prokaryotes (ICNP). Here we summarize the development of the SeqCode, a code of nomenclature under which genome sequences serve as nomenclatural types. This code enables valid publication of names of prokaryotes based upon isolate genome, metagenome-assembled genome or single-amplified genome sequences. Otherwise, it is similar to the ICNP with regard to the formation of names and rules of priority. It operates through the SeqCode Registry (https://seqco.de/), a registration portal through which names and …