Chemicals and Drugs Commons^™

Enhancement Of Deep Learning Protein Structure Prediction, Ruoming Shen

Modeling, Simulation and Visualization Student Capstone Conference

Protein modeling is a rapidly expanding field with valuable applications in the pharmaceutical industry. Accurate protein structure prediction facilitates drug design, as extensive knowledge about the atomic structure of a given protein enables scientists to target that protein in the human body. However, protein structure identification in certain types of protein images remains challenging, with medium resolution cryogenic electron microscopy (cryo-EM) protein density maps particularly difficult to analyze. Recent advancements in computational methods, namely deep learning, have improved protein modeling. To maximize its accuracy, a deep learning model requires copious amounts of up-to-date training data.

This project explores DeepSSETracer, a …

Prosaas And Neurodegenerative Diseases, Cydney Battle

OUR Journal: ODU Undergraduate Research Journal

Neurodegenerative diseases such as Alzheimer’s disease, prion diseases, Huntington’s disease, and Parkinson’s disease undeniably wreak havoc on the system of the body. The catastrophic effects of neurodegenerative diseases are felt by the reality of being incurable and the resulting effect of the progressive degeneration of the individual’s physical and mental stature. Through continuous research, experimentation, and an understanding of how neurodegenerative diseases develop and function, scientific tactics against the development and progression of these diseases will be uncovered. The abnormal aggregation of proteins is largely attributed to the development of neurodegenerative diseases. In the instance of abnormal protein aggregation, the …

Identification Of Proteins Involved In Cell Membrane Permeabilization By Nanosecond Electric Pulses (Nsep), Giedre Silkuniene, Uma Mangalanathan, Alessandra Rossi, Peter A. Mollica, Andrei G. Pakhomov, Olga N. Pakhomova

Bioelectrics Publications

The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in the cell membrane disrupted by nsEP (20 or 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs) of 316 genes encoding for membrane proteins in U937 human monocytes stably expressing Cas9 nuclease. The extent of membrane permeabilization by nsEP was measured by the uptake of Yo-Pro-1 (YP) dye and compared to sham-exposed KOs and control cells transduced with a non-targeting (scrambled) gRNA. Only two KOs, for SCNN1A and CLCA1 genes, showed a statistically significant reduction in …

Para-Methoxybenzylidene Acetal-Protected D-Glucosamine Derivatives As Ph-Responsive Gelators And Their Applications For Drug Delivery, Jonathan Bietsch, Logan Baker, Anna Duffney, Alice Mao, Mary Foutz, Cheandri Ackermann, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Carbohydrate-based low molecular weight gelators (LMWGs) are compounds with the capability to self-assemble into complex molecular networks within a solvent, leading to solvent immobilization. This process of gel formation depends on noncovalent interactions, including Van der Waals, hydrogen bonding, and π–π stacking. Due to their potential applications in environmental remediation, drug delivery, and tissue engineering, these molecules have emerged as an important area of research. In particular, various 4,6-O-benzylidene acetal-protected D-glucosamine derivatives have shown promising gelation abilities. In this study, a series of C-2-carbamate derivatives containing a para-methoxy benzylidene acetal functional group were synthesized and characterized. These compounds exhibited good …

The Effect Of Metalation On Antimicrobial Piscidins Imbedded In Normal And Oxidized Lipid Bilayers, Ana Dreab, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

Metalation of the N-terminal Amino Terminal Cu(II)- and Ni(II)-binding (ATCUN) motif may enhance the antimicrobial properties of piscidins. Molecular dynamics simulations of free and nickelated piscidins 1 and 3 (P1 and P3) were performed in 3 : 1 POPC/POPG and 2.6 : 1 : 0.4 POPC/POPG/aldo-PC bilayers (POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine: POPG, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol; aldo-PC, 1-palmitoyl-2-(9′-oxo-nonanoyl)-sn-glycero-3-phosphocholine) bilayer models. Nickel(II) binding decreases the conformation dynamics of the ATCUN motif and lowers the charge of the N-terminus to allow it to embed deeper in the bilayer without significantly changing the overall depth due to interactions of the charged half-helix …

Synthesis And Self-Assembling Properties Of Carbohydrate- And Diarylethene-Based Photoswitchable Molecular Gelators, Pramod Aryal, Joedian Morris, Surya B. Adhikari, Jonathan Bietsch, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Carbohydrate-based low-molecular-weight gelators are interesting new materials with many potential applications. These compounds can be designed to include multiple stimuli-responsive functional groups. In this study, we designed and synthesized several chemically responsive bola-glycolipids and dimeric carbohydrate- and diarylethene-based photoswitchable derivatives. The dimeric glycolipids formed stable gels in a variety of solvent systems. The best performing gelators in this series contained decanedioic and dithienylethene (DTE) spacers, which formed gels in eight and nine of the tested solvents, respectively. The two new DTE-containing esters possessed interesting photoswitching properties and DTE derivative 7 was found to have versatile gelation properties in many solvents, …

Identifying The Serious Clinical Outcomes Of Adverse Reactions To Drugs By A Multi-Task Deep Learning Framework, Haochen Zhao, Peng Ni, Qichang Zhao, Xiao Liang, Di Ai, Shannon Erhardt, Jun Wang, Yaohang Li, Jiianxin Wang

Computer Science Faculty Publications

Adverse Drug Reactions (ADRs) have a direct impact on human health. As continuous pharmacovigilance and drug monitoring prove to be costly and time-consuming, computational methods have emerged as promising alternatives. However, most existing computational methods primarily focus on predicting whether or not the drug is associated with an adverse reaction and do not consider the core issue of drug benefit-risk assessment-whether the treatment outcome is serious when adverse drug reactions occur. To this end, we categorize serious clinical outcomes caused by adverse reactions to drugs into seven distinct classes and present a deep learning framework, so-called GCAP, for predicting the …

An Acute Respiratory Distress Syndrome Drug Development Collaboration Stimulated By The Virginia Drug Discovery Consortium, John S. Lazo, Ruben M.L. Colunga-Biancatelli, Pavel A. Solopov, John D. Catravas

Bioelectrics Publications

The genesis of most older medicinal agents has generally been empirical. During the past one and a half centuries, at least in the Western countries, discovering and developing drugs has been primarily the domain of pharmaceutical companies largely built upon concepts emerging from organic chemistry. Public sector funding for the discovery of new therapeutics has more recently stimulated local, national, and international groups to band together and focus on new human disease targets and novel treatment approaches. This Perspective describes one contemporary example of a newly formed collaboration that was simulated by a regional drug discovery consortium. University of Virginia, …

A Quality Improvement Project To Improve Management Of Urinary Tract Infections In A System Of Pediatric Urgent Care Centers, Benjamin Klick, Tammy Speerhas, Jessica Parrott, Jeffrey Bobrowitz, Anne Mcevoy, Debra Conrad, Theresa Guins

Nursing Faculty Publications

Background and objective: Urinary tract infections (UTIs) are a common problem in pediatric urgent care medicine. There are multiple quality improvement (QI) projects related to the management of UTIs documented in the pediatric literature. We developed a project to decrease the prescribing of ultimately unneeded antibiotics for possible UTIs in a pediatric urgent care setting. A similar project has not been described in the pediatric literature.

Methods: We first reviewed the charts of patients presenting to a system of pediatric urgent care centers with a possible UTI over a 2-year period. We then launched a QI project with three plan, …

Synthesis Of A Series Of Trimeric Branched Glycoconjugates And Their Applications For Supramolecular Gels And Catalysis, Jonathan Bietsch, Anji Chen, Dan Wang, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Carbohydrate-derived molecular gelators have found many practical applications as soft materials. To better understand the structure and molecular gelation relationship and further explore the applications of sugar-based gelators, we designed and synthesized eight trimeric branched sugar triazole derivatives and studied their self-assembling properties. These included glucose, glucosamine, galactose, and maltose derivatives. Interestingly, the gelation properties of these compounds exhibited correlations with the peripheral sugar structures. The maltose derivative did not form gels in the tested solvents, but all other compounds exhibited gelation properties in at least one of the solvents. Glucose derivatives showed superior performance, followed by glucosamine derivatives. They …

Enhancing The Conformational Stability Of The Cl-Par-4 Tumor Suppressor Via Site-Directed Mutagenesis, Samjhana Pandey, Krishna K. Raut, Andrea M. Clark, Antoine Baudin, Lamya Djemri, David S. Libich, Komala Ponniah, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Intrinsically disordered proteins play important roles in cell signaling, and dysregulation of these proteins is associated with several diseases. Prostate apoptosis response-4 (Par-4), an approximately 40 kilodalton proapoptotic tumor suppressor, is a predominantly intrinsically disordered protein whose downregulation has been observed in various cancers. The caspase-cleaved fragment of Par-4 (cl-Par-4) is active and plays a role in tumor suppression by inhibiting cell survival pathways. Here, we employed site-directed mutagenesis to create a cl-Par-4 point mutant (D313K). The expressed and purified D313K protein was characterized using biophysical techniques, and the results were compared to that of the wild-type (WT). We have …

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany B. Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Human Movement Sciences & Special Education Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal …

Detection And Quantification Of Antiviral Drug Tenofovir Using Silver Nanoparticles And Surface Enhanced Raman Spectroscopy (Sers) With Spatially Resolved Hotspot Selection, Marguerite R. Butler, Jana Hrncirova, Terry A. Jacot, Sucharita Dutta, Meredith R. Clark, Gustavo F. Doncel, John B. Cooper

Chemistry & Biochemistry Faculty Publications

This study introduces a convenient and ultra-sensitive method of detection and quantification of the antiviral drug, tenofovir (TFV), by surface-enhanced Raman spectroscopy (SERS). Novel spatially resolved instrumentation for spectral acquisition and subsequent statistical analysis for hot spot selection was developed for convenient quantification of TFV in an aqueous matrix. Methods of statistical analysis include the use of partial least squares (PLS) regression vector analysis and spectral ranking by quality indices computed using CHAOS theory. Hydroxylamine-reduced Ag colloidal nanoparticles evaporated to dryness on an aluminum well-plate were used as the SERS substrate. To our knowledge, quantification of TFV down to 25 …

Msdrp: A Deep Learning Model Based On Multisource Data For Predicting Drug Response, Haochen Zhao, Xiaoyu Zhang, Qichang Zhao, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Cancer heterogeneity drastically affects cancer therapeutic outcomes. Predicting drug response in vitro is expected to help formulate personalized therapy regimens. In recent years, several computational models based on machine learning and deep learning have been proposed to predict drug response in vitro. However, most of these methods capture drug features based on a single drug description (e.g. drug structure), without considering the relationships between drugs and biological entities (e.g. target, diseases, and side effects). Moreover, most of these methods collect features separately for drugs and cell lines but fail to consider the pairwise interactions between drugs and cell …

An Approach To Developing Benchmark Datasets For Protein Secondary Structure Segmentation From Cryo-Em Density Maps, Thu Nguyen, Yongcheng Mu, Jiangwen Sun, Jing He

Computer Science Faculty Publications

More and more deep learning approaches have been proposed to segment secondary structures from cryo-electron density maps at medium resolution range (5--10Å). Although the deep learning approaches show great potential, only a few small experimental data sets have been used to test the approaches. There is limited understanding about potential factors, in data, that affect the performance of segmentation. We propose an approach to generate data sets with desired specifications in three potential factors - the protein sequence identity, structural contents, and data quality. The approach was implemented and has generated a test set and various training sets to study …

Progenitor Cell Isolation From Mouse Epididymal Adipose Tissue And Sequencing Library Construction, Qianglin Liu, Chaoyang Li, Yuxia Li, Leshan Wang, Xujia Zhang, Buhao Deng, Peidong Gao, Mohammad Shiri, Fozi Alkaifi, Junxing Zhao, Jacqueline M. Stephens, Constantine A. Simintiras, Joseph Francis, Jiangwen Sun, Xing Fu

Computer Science Faculty Publications

Here, we present a protocol to isolate progenitor cells from mouse epididymal visceral adipose tissue and construct bulk RNA and assay for transposase-accessible chromatin with sequencing (ATAC-seq) libraries. We describe steps for adipose tissue collection, cell isolation, and cell staining and sorting. We then detail procedures for both ATAC-seq and RNA sequencing library construction. This protocol can also be applied to other tissues and cell types directly or with minor modifications.

For complete details on the use and execution of this protocol, please refer to Liu et al. (2023).¹

*¹ Liu, Q., Li, C., Deng, B., Gao, P., …