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Coevolution Combined With Molecular Dynamics Simulations Provides Structural And Mechanistic Insights Into The Interactions Between The Integrator Complex Subunits, Bernard Fongang, Yannick N Wadop, Yingjie Zhu, Eric J Wagner, Andrzej Kudlicki, Maga Rowicka

Faculty, Staff and Student Publications

Finding the 3D structure of large, multi-subunit complexes is difficult, despite recent advances in cryo-EM technology, due to remaining challenges to expressing and purifying subunits. Computational approaches that predict protein-protein interactions, including Direct Coupling Analysis (DCA), represent an attractive alternative for dissecting interactions within protein complexes. However, they are readily applicable only to small proteins due to high computational complexity and a high number of false positives. To solve this problem, we proposed a modified DCA approach, a powerful tool to predict the most likely interfaces of protein complexes. Since our modified approach cannot provide structural and mechanistic details of …

Social Determinant Of Health Impact On Diabetes Device Use And Clinical Outcomes In Youth With Type 1 Diabetes, Emily R Crain, Ryan Ramphul, Ashley M Butler, Xiaofan Huang, Charles G Minard, Maria J Redondo, Daniel J Desalvo

Faculty, Staff and Student Publications

Background: Youth with Type 1 diabetes (T1D) who are Black, Hispanic, or lower socioeconomic status (SES) have lower rates of diabetes device use, higher hemoglobin A1c (HbA1c), and higher rates of diabetic ketoacidosis (DKA). However, the associations of individual-level social determinants of health (SDoH) and neighborhood-level factors with device use and clinical outcomes are unknown. Area deprivation index (ADI) is a neighborhood level measure of SES reported in deciles (range 1-10 with 10 representing most deprived neighborhood).

Methods: We evaluated the association of ADI and other SDoH factors with pump/continuous glucose monitor (CGM) use, HbA1c, and DKA in 1,461 youth …

Hpv-Related Oropharyngeal Cancer Early Detection In Gay And Bisexual Men Is An “Orphan” Practice: A Qualitative Analysis Among Healthcare Providers, I Niles Zoschke, Sarah L Bennis, J Michael Wilkerson, Cynthia L Stull, Alan G Nyitray, Samir S Khariwala, C Mark Nichols, B R Simon Rosser, Charlene Flash, Michael W Ross

Faculty, Staff and Student Publications

Introduction: Among US men, oropharyngeal cancer (cancer of the back of the mouth and throat) is the 8th most common cancer. If detected early, human papillomavirus (HPV)-16-associated oropharyngeal cancer has a high 5-year survival rate. Risk factors such as high numbers of oral sex partners, disparities in smoking and drinking, and low rates of HPV vaccination may put gay and bisexual men at even higher risk for oropharyngeal cancer.

Methods: We recruited 21 healthcare providers in Minneapolis-St. Paul, Minnesota and Houston, Texas to participate in semi-structured interviews. Nurses, physician assistants, dental hygienists, and dentists were asked about their clinical experiences …

Influences Of Race/Ethnicity In Periodontal Treatment Response And Bacterial Distribution, A Cohort Pilot Study, Bing-Yan Wang, Grayson Burgardt, Kavitha Parthasarathy, Daniel K Ho, Robin L Weltman, Gena D Tribble, Jianming Hong, Stanley Cron, Hua Xie

Faculty, Staff and Student Publications

OBJECTIVES: Periodontitis disproportionately affects different racial and ethnic populations. We have previously reported the higher levels of

METHODS: This prospective cohort pilot study was carried out in an academic setting, at the School of Dentistry, University of Texas Health Science Center at Houston. Dental plaque was collected from a total of 75 African Americans, Caucasians and Hispanics periodontitis patients in a 3-year period. Quantitation of

RESULTS: The gains in clinical attachment levels after treatment significantly differed amongst the 3 groups-Caucasians responded most favorably, followed by African-Americans, lastly Hispanics, while numbers of

CONCLUSION: Differential response to nonsurgical periodontal treatment and distribution …

Identification Of Microbiological Factors Associated With Periodontal Health Disparities, Bing-Yan Wang, Aize Cao, Meng-Hsuan Ho, Derek Wilus, Sally Sheng, Hsiu-Wan Meng, Elissa Guerra, Jianming Hong, Hua Xie

Faculty, Staff and Student Publications

The present study aimed at identifying risk factors associated with periodontitis development and periodontal health disparities with emphasis on differential oral microbiota. The prevalence of periodontitis is recently rising dentate adults in the US, which presents a challenge to oral health and overall health. The risk of developing periodontitis is higher in African Americans (AAs), and Hispanic Americans (HAs) than in Caucasian Americans (CAs). To identify potentially microbiological determinations of periodontal health disparities, we examined the distribution of several potentially beneficial and pathogenic bacteria in the oral cavities of AA, CA, and HA study participants. Dental plaque samples from 340 …

Editorial: Period Poverty, Lea Sacca, Christine Margaret Markham, Jhumka Gupta, Melissa Peskin

Faculty, Staff and Student Publications

No abstract provided.

Assessing Pandemic Preparedness, Response, And Lessons Learned From The Covid-19 Pandemic In Four South American Countries: Agenda For The Future, Andrea Ramírez Varela, Michael Touchton, J Jaime Miranda, Juliana Mejía Grueso, Rachid Laajaj, Gabriel Carrasquilla, Martha Vives Florez, Ana María Vesga Gaviria, Ana María Ortiz Hoyos, Esteban Orlando Vanegas Duarte, Alejandra Velásquez Morales, Nubia Velasco, Silvia Restrepo Restrepo

Faculty, Staff and Student Publications

INTRODUCTION: The COVID-19 pandemic emerged in a context that lacked adequate prevention, preparedness, and response (PPR) activities, and global, regional, and national leadership. South American countries were among world's hardest hit by the pandemic, accounting for 10.1% of total cases and 20.1% of global deaths.

METHODS: This study explores how pandemic PPR were affected by political, socioeconomic, and health system contexts as well as how PPR may have shaped pandemic outcomes in Argentina, Brazil, Colombia, and Peru. We then identify lessons learned and advance an agenda for improving PPR capacity at regional and national levels. We do this through a …

Editorial: The Impact Of Inflammation On The Oral Microbiome, Chun-Teh Lee, Loreto Abusleme, Thomas E Van Dyke

Faculty, Staff and Student Publications

No abstract provided.

Toward A More Comprehensive Understanding Of Organizational Influences On Implementation: The Organization Theory For Implementation Science Framework, Sarah A Birken, Cheyenne R Wagi, Alexandra G Peluso, Michelle C Kegler, Jure Baloh, Prajakta Adsul, Maria E Fernandez, Manal Masud, Terry T-K Huang, Matthew Lee, Mary Wangen, Per Nilsen, Miriam Bender, Mimi Choy-Brown, Grace Ryan, Aliza Randazzo, Linda K Ko

Faculty, Staff and Student Publications

Introduction: Implementation is influenced by factors beyond individual clinical settings. Nevertheless, implementation research often focuses on factors related to individual providers and practices, potentially due to limitations of available frameworks. Extant frameworks do not adequately capture the myriad organizational influences on implementation. Organization theories capture diverse organizational influences but remain underused in implementation science. To advance their use among implementation scientists, we distilled 70 constructs from nine organization theories identified in our previous work into theoretical domains in the Organization Theory for Implementation Science (OTIS) framework.

Methods: The process of distilling organization theory constructs into domains involved concept mapping and …

Peripheral Calcifying Odontogenic Cyst: A Case Report And Comprehensive Review Of 60 Years Of Literature, Sally Sheng, Nicholas Tipton, Jennifer Chang, Hsiu-Wan Meng, Gena D Tribble

Faculty, Staff and Student Publications

Peripheral Calcifying Odontogenic Cyst (PCOC) is the extraosseous form of calcifying odontogenic cyst that is limited to peripheral soft tissue without bony involvement. This case report presents a case of PCOC manifested as a progressive growth of gingival mass in a young male treated with excisional biopsy. Histological examination confirmed diagnosis of PCOC with presence of characteristic ghost cells and sporadic calcifications. No recurrence of the lesion and no complication were noted at three-year follow-up. Review of available literature on PCOC noted a predilection of occurrence in the mandible (61%) and in the anterior area of the jaws (58%). Mean …

Comorbidity Network Analysis Using Graphical Models For Electronic Health Records, Bo Zhao, Sarah Huepenbecker, Gen Zhu, Suja S Rajan, Kayo Fujimoto, Xi Luo

Faculty, Staff and Student Publications

IMPORTANCE: The comorbidity network represents multiple diseases and their relationships in a graph. Understanding comorbidity networks among critical care unit (CCU) patients can help doctors diagnose patients faster, minimize missed diagnoses, and potentially decrease morbidity and mortality.

OBJECTIVE: The main objective of this study was to identify the comorbidity network among CCU patients using a novel application of a machine learning method (graphical modeling method). The second objective was to compare the machine learning method with a traditional pairwise method in simulation.

METHOD: This cross-sectional study used CCU patients' data from Medical Information Mart for the Intensive Care-3 (MIMIC-3) dataset, …

Ai-Drugnet: A Network-Based Deep Learning Model For Drug Repurposing And Combination Therapy In Neurological Disorders, Xingxin Pan, Jun Yun, Zeynep H Coban Akdemir, Xiaoqian Jiang, Erxi Wu, Jason H Huang, Nidhi Sahni, S Stephen Yi

Faculty, Staff and Student Publications

Discovering effective therapies is difficult for neurological and developmental disorders in that disease progression is often associated with a complex and interactive mechanism. Over the past few decades, few drugs have been identified for treating Alzheimer's disease (AD), especially for impacting the causes of cell death in AD. Although drug repurposing is gaining more success in developing therapeutic efficacy for complex diseases such as common cancer, the complications behind AD require further study. Here, we developed a novel prediction framework based on deep learning to identify potential repurposed drug therapies for AD, and more importantly, our framework is broadly applicable …

Gain-Of-Function Variomics And Multi-Omics Network Biology For Precision Medicine, Mark M Li, Sharad Awasthi, Sumanta Ghosh, Deepa Bisht, Zeynep H Coban Akdemir, Gloria M Sheynkman, Nidhi Sahni, S Stephen Yi

Faculty, Staff and Student Publications

Traditionally, disease causal mutations were thought to disrupt gene function. However, it becomes more clear that many deleterious mutations could exhibit a "gain-of-function" (GOF) behavior. Systematic investigation of such mutations has been lacking and largely overlooked. Advances in next-generation sequencing have identified thousands of genomic variants that perturb the normal functions of proteins, further contributing to diverse phenotypic consequences in disease. Elucidating the functional pathways rewired by GOF mutations will be crucial for prioritizing disease-causing variants and their resultant therapeutic liabilities. In distinct cell types (with varying genotypes), precise signal transduction controls cell decision, including gene regulation and phenotypic output. …

A Novel Bayesian Spatial-Temporal Approach To Quantify Sars-Cov-2 Testing Disparities For Small Area Estimation, Cici Bauer, Xiaona Li, Kehe Zhang, Miryoung Lee, Esmeralda Guajardo, Susan Fisher-Hoch, Joseph Mccormick, Maria E Fernandez, Belinda Reininger

Faculty, Staff and Student Publications

Objectives. To propose a novel Bayesian spatial–temporal approach to identify and quantify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing disparities for small area estimation.

Methods. In step 1, we used a Bayesian inseparable space–time model framework to estimate the testing positivity rate (TPR) at geographically granular areas of the census block groups (CBGs). In step 2, we adopted a rank-based approach to compare the estimated TPR and the testing rate to identify areas with testing deficiency and quantify the number of needed tests. We used weekly SARS-CoV-2 infection and testing surveillance data from Cameron County, Texas, between March 2020 …

Genetic Associations Between Sleep Traits And Cognitive Ageing Outcomes In The Hispanic Community Health Study/Study Of Latinos, Yuan Zhang, Michael Elgart, Einat Granot-Hershkovitz, Heming Wang, Wassim Tarraf, Alberto R Ramos, Ariana M Stickel, Donglin Zeng, Tanya P Garcia, Fernando D Testai, Sylvia Wassertheil-Smoller, Carmen R Isasi, Martha L Daviglus, Robert Kaplan, Myriam Fornage, Charles Decarli, Susan Redline, Hector M González, Tamar Sofer

Faculty, Staff and Student Publications

BACKGROUND: Sleep phenotypes have been reported to be associated with cognitive ageing outcomes. However, there is limited research using genetic variants as proxies for sleep traits to study their associations. We estimated associations between Polygenic Risk Scores (PRSs) for sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnoea (OSA) and measures of cogntive ageing in Hispanic/Latino adults.

METHODS: We used summary statistics from published genome-wide association studies to construct PRSs representing the genetic basis of each sleep trait, then we studied the association of the PRSs of the sleep phenotypes with cognitive outcomes in the Hispanic Community Healthy Study/Study of …

Enabling Structural Resilience Of Street-Involved Children And Youth In Kenya: Reintegration Outcomes And The Flourishing Community Model, Michael L Goodman, Sarah E Seidel, Andrew Springer, Aleisha Elliott, Christine Markham, Hani Serag, Philip Keiser, Ben Raimer, Lauren Raimer-Goodman, Christine Gatwiri, Kelvin Munene, Stanley Gitari

Faculty, Staff and Student Publications

Introduction: Millions of children and youth live on city streets across the globe, vulnerable to substance use, abuse, material and structural neglect. Structural resilience, the re-establishment of access to structural goods within a society such as housing, education, and healthcare following some interruption, provides an orientation for research and interventional efforts with street-involved children and youth (SICY). Further, a structural resilience framework supports organizing interactions between levels and sectors of a socio-ecology.

Methods: Following the expressed interests of Kenyan SICY, and consistent with emerging policy interests at national and global levels, we assess reintegration trajectories of Kenyan SICY (n …

Pregnancy-Related Covid Worry, Depressive Symptom Severity, And Mediation Through Sleep Disturbance In A Low-Income, Primarily Latinx Population In California’S Central Valley, Jennifer N Felder, Patience A Afulani, Kimberly Coleman-Phox, Serwaa S Omowale, Charles E Mcculloch, Lauren Lessard, Miriam Kuppermann

Faculty, Staff and Student Publications

Purpose: This study (1) assessed the psychometric properties of a pregnancy-related COVID worry scale, (2) explored variations in pregnancy-related COVID worry over the course of the pandemic, and (3) examined associations between pregnancy-related COVID worry and depressive symptom severity, and evaluated sleep disturbance as a mediator.

Methods: Data were drawn from an ongoing randomized trial comparing the effectiveness of two enhanced forms of prenatal care. The current analysis includes baseline pre-randomization data collected from participants who enrolled November 2020-November 2021 (n = 201). Participants were pregnant individuals with low income and primarily Latinx.

Results: Our 7-item scale was valid and …

Maternal Perceptions Of Vaccinating Boys Against Human Papillomavirus (Hpv) In Seoul, South Korea: A Descriptive Exploratory Qualitative Study, Jihye Choi, Christine Markham, Irene Tamí-Maury, Sooyoun Kim, Paula Cuccaro

Faculty, Staff and Student Publications

Human Papillomavirus (HPV) vaccination is of paramount importance to reduce HPV-associated cancers in both genders. In South Korea, the prophylactic vaccine is recognized as prevention of cervical cancer with little attention given to male HPV vaccination. The purpose of this study was to explore perceptions of male HPV vaccination and underlying factors for vaccine hesitancy among mothers of unvaccinated boys in Seoul, Korea using a qualitative method. We used a purposive sampling strategy to recruit mothers of unvaccinated middle school-aged boys living in one of the 25 districts in Seoul, supplemented by a snowball sampling approach. We conducted one-on-one telephone …

A Narrative Review Of The Lesser Known Medications For Treatment Of Restless Legs Syndrome And Pathogenetic Implications For Their Use, Paul G Yeh, Karen Spruyt, Lourdes M Delrosso, Arthur S Walters

Faculty, Staff and Student Publications

BACKGROUND: There are several well-known treatments for Restless Legs Syndrome (RLS), including dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin and its analogs, pregabalin), oral or intravenous iron, opioids and benzodiazepines. However, in clinical practice, treatment is sometimes limited due to incomplete response or side effects and it is necessary to be aware of other treatment options for RLS, which is the purpose of this review.

METHODS: We performed a narrative review detailing all of the lesser known pharmacological treatment literature on RLS. The review purposefully excludes well-established, well-known treatments for RLS which are widely accepted as treatments for RLS in …

From The National To The Local: Issues Of Trust And A Model For Community-Academic-Engagement, Olufunmilayo Chinekezi, Lauri Andress, Etsemaye P Agonafer, Susan Massick, Sarah Piepenbrink, Karey M Sutton, Philip M Alberti, Desiree De La Torre, Shannon Guillot-Wright, Marshala Lee

Faculty, Staff and Student Publications

Inequities in health and health care in the United States have persisted for decades, and the impacts on equity from the COVID-19 pandemic were no exception. In addition to the disproportionate burden of the disease across various populations, the pandemic posed several challenges, which exacerbated these existing inequities. This has undoubtedly contributed to deeply rooted public mistrust in medical research and healthcare delivery, particularly among historically and structurally oppressed populations. In the summer of 2020, given the series of social injustices posed by the pandemic and highly publicized incidents of police brutality, notably the murder of George Floyd, the Association …

The Predictive Value Of Coronary Microvascular Dysfunction For Left Ventricular Reverse Remodelling In Dilated Cardiomyopathy, Ao Kan, Yinping Leng, Shuhao Li, Fang Lin, Qimin Fang, Xinwei Tao, Mengyao Hu, Lianggeng Gong

Faculty, Staff and Student Publications

AIMS: to evaluate the degree of coronary microvascular dysfunction (CMD) in dilated cardiomyopathy (DCM) patients by cardiac magnetic resonance (CMR) first-pass perfusion parameters and to examine the correlation between myocardial perfusion and left ventricle reverse remodelling (LVRR).

METHODS: In this study, 94 DCM patients and 35 healthy controls matched for age and sex were included. Myocardial perfusion parameters, including upslope, time to maximum signal intensity (Time

RESULTS: With a median follow-up period of 12 months [interquartile range (IQR), 8-13], 41 DCM patients (44%) achieved LVRR. Compared with healthy controls, DCM patients presented CMD with reduced upslope, SI

CONCLUSIONS: CMD could …

A Case Of Successful Treatment Of Recurrent Urinary Tract Infection By Extended-Spectrum Β-Lactamase Producing, Naomi Bier, Blake Hanson, Zhi-Dong Jiang, Herbert L Dupont, Cesar A Arias, William R Miller

Faculty, Staff and Student Publications

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing

Subendocardial And Transmural Myocardial Ischemia: Clinical Characteristics, Prevalence, And Outcomes With And Without Revascularization, K Lance Gould, Tung Nguyen, Richard Kirkeeide, Amanda E Roby, Linh Bui, Danai Kitkungvan, Monica B Patel, Mohammad Madjid, Mary Haynie, Dejian Lai, Ruosha Li, Jagat Narula, Nils P Johnson

Faculty, Staff and Student Publications

BACKGROUND: Subendocardial ischemia is commonly diagnosed but not quantified by imaging.

OBJECTIVES: This study sought to define size and severity of subendocardial and transmural stress perfusion deficits, clinical associations, and outcomes.

METHODS: Regional rest-stress perfusion in mL/min/g, coronary flow reserve, coronary flow capacity (CFC), relative stress flow, subendocardial stress-to-rest ratio and stress subendocardial-to-subepicardial ratio as percentage of left ventricle were measured by positron emission tomography (PET) with rubidium Rb 82 and dipyridamole stress in serial 6,331 diagnostic PETs with prospective 10-year follow-up for major adverse cardiac events with and without revascularization.

RESULTS: Of 6,331 diagnostic PETs, 1,316 (20.7%) had severely …

Corrigendum: Editorial: Period Poverty, Lea Sacca, Christine Margaret Markham, Jhumka Gupta, Melissa Peskin

Faculty, Staff and Student Publications

This corrects the article "Editorial: Period poverty" in volume 5, 1140981.

Novornabreak: Local Assembly For Novel Splice Junction And Fusion Transcript Detection From Rna-Seq Data, Yukun Tan, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jun Ma, Kun Hee Kim, Marc Jan Bonder, Xinghua Shi, Charles Lee, Zechen Chong, Ken Chen

Faculty, Staff and Student Publications

We present novoRNABreak, a unified framework for cancer specific novel splice junction and fusion transcript detection in RNA-seq data obtained from human cancer samples. novoRNABreak is based on a local assembly model, which offers a tradeoff between the alignment-based and de novo whole transcriptome assembly (WTA) methods. This approach is accurate and sensitive in assembling novel junctions that are difficult to directly align or have multiple alignments. Additionally, it is more efficient due to the strategy that focuses on junctions rather than full length transcripts. The performance of novoRNABreak is demonstrated by a comprehensive set of experiments using synthetic data …

Automated Brain Metastases Segmentation With A Deep Dive Into False-Positive Detection, Hamidreza Ziyaee, Carlos E Cardenas, D Nana Yeboa, Jing Li, Sherise D Ferguson, Jason Johnson, Zijian Zhou, Jeremiah Sanders, Raymond Mumme, Laurence Court, Tina Briere, Jinzhong Yang

Faculty, Staff and Student Publications

Purpose: The clinical management of brain metastases after stereotactic radiosurgery (SRS) is difficult, because a physician must review follow-up magnetic resonance imaging (MRI) scans to determine treatment outcome, which is often labor intensive. The purpose of this study was to develop an automated framework to contour brain metastases in MRI to help treatment planning for SRS and understand its limitations.

Methods and materials: Two self-adaptive nnU-Net models trained on postcontrast 3-dimensional T1-weighted MRI scans from patients who underwent SRS were analyzed. Performance was evaluated by computing positive predictive value (PPV), sensitivity, and Dice similarity coefficient (DSC). The training and testing …

Pathologic And Molecular Insights In Nodal T-Follicular Helper Cell Lymphomas, Mario L Marques-Piubelli, Catalina Amador, Francisco Vega

Faculty, Staff and Student Publications

T-follicular helper (TFH) cells are one of the T-cell subsets with a critical role in the regulation of germinal center (GC) reactions. TFH cells contribute to the positive selection of GC B-cells and promote plasma cell differentiation and antibody production. TFH cells express a unique phenotype characterized by PD-1hi, ICOShi, CD40Lhi, CD95hi, CTLAhi, CCR7lo, and CXCR5hi . Three main subtypes of nodal TFH lymphomas have been described: 1) angioimmunoblastic-type, 2) follicular-type, and 3) not otherwise specified (NOS). The diagnosis of these neoplasms can be challenging, and it is rendered based on a combination of clinical, laboratory, histopathologic, immunophenotypic, and molecular …

When Guilt Works: A Comprehensive Meta-Analysis Of Guilt Appeals, Wei Peng, Qian Huang, Bingjing Mao, Di Lun, Ekaterina Malova, Jazmyne V Simmons, Nick Carcioppolo

Faculty, Staff and Student Publications

Introduction: Guilt appeals are widely used as a persuasive approach in various areas of practice. However, the strength and direction of the persuasive effects of guilt appeals are mixed, which could be influenced by theoretical and methodological factors.

Method: The present study is a comprehensive meta-analysis of 26 studies using a random-effects model to assess the persuasive effects of guilt appeals. In total, 127 effect sizes from seven types of persuasive outcomes (i.e., guilt, attitude, behavior, behavioral intention, non-guilt emotions, motivation, and cognition) were calculated based on 7,512 participants.

Results: The analysis showed a small effect size of guilt appeals …

Sociodemographic Differences In Menthol Cigarette Use In The United States, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

Background: Menthol cigarette use is associated with higher smoking initiation and reduced smoking cessation. We investigated sociodemographic differences in menthol and nonmenthol cigarette use in the United States.

Methods: We used the most recent available data from the May 2019 wave of the nationally-representative Tobacco Use Supplement to the Current Population Survey. The survey weights were used to estimate the national prevalence of individuals who currently smoke among individuals who use menthol and nonmenthol cigarettes. Survey-weighted logistic regression methods were used to estimate the association of menthol cigarette use with formerly smoking cigarettes and attempting to quit within the past …

Applying Ht-Saxs To Chemical Ligand Screening, Chris A Brosey, Runze Shen, Davide Moiani, Darin E Jones, Kathryn Burnett, Greg L Hura, John A Tainer

Faculty, Staff and Student Publications

Chemical probes are invaluable tools for investigating essential biological processes. Understanding how small-molecule probes engage biomolecular conformations is critical to developing their functional selectivity. High-throughput solution X-ray scattering is well-positioned to profile target-ligand complexes during probe development, bringing conformational insight and selection to traditional ligand binding assays. Access to high-quality synchrotron SAXS datasets and high-throughput data analysis now allows routine academic users to incorporate conformational information into small-molecule development pipelines. Here we describe a general approach for benchmarking and preparing HT-SAXS chemical screens from small fragment libraries. Using the allosteric oxidoreductase Apoptosis-Inducing Factor (AIF) as an exemplary system, we illustrate …