VTechWorks Repository :: Browsing by Author "Brown, Anne M."

Browsing by Author "Brown, Anne M."

Now showing 1 - 20 of 52

2018 R & I Annual Report
Griffin, Julie; Hilal, Amr E.; Brown, Anne M.; Petters, Jonathan L.; Porter, Nathaniel D.; McMillan, Gail; Cross, Carrie; Pannabecker, Virginia; Smith, Erin M. (Virginia Tech, 2018)
This is the 2018 annual report for the Research & Informatics division at University Libraries.
A Bioinformatics Approach to Identifying Radical SAM (S-Adenosyl-L-Methionine) Enzymes
Gagliano, Elisa (Virginia Tech, 2020-06-03)
Radical SAM enzymes are ancient, essential enzymes. They perform radical chemical reactions in virtually all living organisms and are involved in producing antibiotics, generating greenhouse gases, human health, and likely many other essential roles that have yet to be established. A wide variety of reactions have been characterized from this group of enzymes, including hydrogen abstractions, the transferring of methylthio groups, complex cyclization and rearrangement reactions, and others. However, many radical SAM enzymes have yet to be identified or characterized. There have been great leaps forward in the amount of enzyme sequences that are available in public databases, but experiments to investigate what chemical reactions the enzymes perform take a great deal of time. In our work, we utilize Hidden Markov Models to identify possible radical SAM enzymes and predict their possible functions through BLAST alignments and homology modelling. We also explore their distribution across the tree of life and determine how it is correlated with organism oxygen tolerances, because the core iron-sulfur cluster is oxygen sensitive. Trends in the abundances of radical SAM enzymes depending on oxygen tolerances were more apparent in prokaryotes than in eukaryotes. Although eukaryotes tend to have fewer radical SAM enzymes than prokaryotes, we were able to analyze uncharacterized radical SAM enzymes from both an aerobic eukaryote (Entamoeba histolytica) and a eukaryote capable of oxygenic photosynthesis (Gossypium barbadense), and predict the reactions they catalyze. This work sets the stage for the functional characterization of these essential yet elusive enzymes in future laboratory experiments.
Characterization and Validation of Arg286 Residue of IL-1RAcP as a Potential Drug Target for Osteoarthritis
Dailing, Angela; Mitchell, Kelsey; Ngoc Vuong; Lee, Kyung Hyeon; Joshi, Reva; Espina, Virginia; Still, Amanda Haymond; Gottschalk, Carter J.; Brown, Anne M.; Paige, Mikell; Liotta, Lance A.; Luchini, Alessandra (2021-02-03)
Osteoarthritis (OA) is the most common form of arthritis and the fastest growing cause of chronic disability in the world. Formation of the ternary IL-1 beta /IL-1R1/IL-1RAcP protein complex and its downstream signaling has been implicated in osteoarthritis pathology. Current OA therapeutic approaches target either the cytokine IL-1 beta or the primary receptor IL-1RI but do not exploit the potential of the secondary receptor IL-1RAcP. Our previous work implicated the Arg286 residue of IL-1RAcP as a key mediator of complex formation. Molecular modeling confirmed Arg286 as a high-energy mediator of the ternary IL-1 beta complex architecture and interaction network. Anti-IL-1RAcP monoclonal antibodies (mAb) targeting the Arg286 residue were created and were shown to effectively reduce the influx of inflammatory cells to damaged joints in a mouse model of osteoarthritis. Inhibitory peptides based on the native sequence of IL-1RAcP were prepared and examined for efficacy at disrupting the complex formation. The most potent peptide inhibitor had an IC50 value of 304 pM in a pull-down model of complex formation, and reduced IL-1 beta signaling in a cell model by 90% at 2 mu M. Overall, therapies that target the Arg286 region surface of IL-1RAcP, and disrupt subsequent interactions with subunits, have the potential to serve as next generation treatments for osteoarthritis.
Computational study of HIV gp120 as a target for polyanionic entry inhibitors: Exploiting the V3 loop region
Hollingsworth, Louis R. IV; Brown, Anne M.; Gandour, Richard D.; Bevan, David R. (PLOS, 2018-01-18)
Multiple approaches are being utilized to develop therapeutics to treat HIV infection. One approach is designed to inhibit entry of HIV into host cells, with a target being the viral envelope glycoprotein, gp120. Polyanionic compounds have been shown to be effective in inhibiting HIV entry, with a mechanism involving electrostatic interactions with the V3 loop of gp120 being proposed. In this study, we applied computational methods to elucidate molecular interactions between the repeat unit of the precisely alternating polyanion, Poly(4,40-stilbenedicarboxylate- alt±maleic acid) (DCSti-alt-MA) and the V3 loop of gp120 from strains of HIV against which these polyanions were previously tested (IIIb, BaL, 92UG037, JR-CSF) as well as two strains for which gp120 crystal structures are available (YU2, 2B4C). Homology modeling was used to create models of the gp120 proteins. Using monomers of the gp120 protein, we applied extensive molecular dynamics simulations to obtain dominant morphologies that represent a variety of open-closed states of the V3 loop to examine the interaction of 112 ligands of the repeating units of DCSti-alt-MA docked to the V3 loop and surrounding residues. Using the distance between the V1/V2 and V3 loops of gp120 as a metric, we revealed through MD simulations that gp120 from the lab-adapted strains (BaL and IIIb), which are more susceptible to inhibition by DCSti-alt-MA, clearly transitioned to the closed state in one replicate of each simulation set, whereas none of the replicates from the Tier II strains (92UG037 and JR-CSF) did so. Docking repeat unit microspecies to the gp120 protein before and after MD simulation enabled identification of residues that were key for binding. Notably, only a few residues were found to be important for docking both before and after MD simulation as a result of the conformational heterogeneity provided by the simulations. Consideration of the residues that were consistently involved in interactions with the ligand revealed the importance of both hydrophilic and hydrophobic moieties of the ligand for effective binding. The results also suggest that polymers of DCSti-alt-MA with repeating units of different configurations may have advantages for therapeutic efficacy.
Computationally and Experimentally Exploring the Type IV Pilus Assembly ATPase for Antivirulence Drug Discovery
Ramos, Jazel Mae Silvela (Virginia Tech, 2023-08-10)
Disease caused by antibiotic resistant (ABR) bacteria has become a widespread global public health issue as humanity's existing collection of effective antibiotics dwindles. ABR bacteria are responsible for approximately 5 million deaths worldwide annually, which is predicted to reach 10 million yearly by 2050. Antivirulence therapeutics have been explored in recent times as another approach to tackling the global ABR pandemic by disrupting the function of virulence factors that promote disease development. The bacterial type IV pilus (T4P) is a prevalent virulence factor in many ABR pathogens, contributing to bacterial pathogenesis by facilitating cell motility, surface adhesion, and biofilm formation. Critically, the T4P facilitates early stages of disease, providing a means to invade and colonize a host. T4P assembly is driven by the PilB/PilF motor ATPase that localizes to the cytoplasmic face of the inner membrane to drive pilus biogenesis by ATP hydrolysis. The thesis work here explores computational and experimental methods for the discovery of antivirulence therapeutics targeting the T4P assembly ATPase PilB. A computational model of Chloracidobacterium thermophilum PilB was generated by homology modeling and molecular docking was performed to analyze the binding characteristics of six anti-PilB inhibitory compounds identified in previous studies. Computational docking aligns with the existing body of work and reveals important protein-ligand interactions and characteristics, particularly involving the ATP binding domain of PilB. This work supports the use of PilB in structure-based virtual screening to identify novel compounds targeting PilB. Additionally, through heterologous expression and chromatography methods, the ATPase core of Neisseria gonorrhoeae PilF was successfully expressed and purified as an active ATPase. This work optimized conditions for its ATPase activity in vitro. Additionally, this thesis documents the experimental attempt to express and purify Clostridioides difficile PilB as an active ATPase. Two of the seven C. difficile PilB variant proteins expressed led to soluble protein while one construct remains to be explored. The results of these studies provide insight for future methodology design for antivirulence therapeutic research targeting the T4P assembly ATPase using both in silico and in vitro methods.
Creating an inclusive, adaptable model for tracking, assessing, and celebrating student success in undergraduate research
MacDonald, Amanda B.; Brown, Anne M.; Swaby, Keri (2020-06)
There is a current need for programmatic and curriculum support for inclusive, university-wide programs that incentives and recognizes students’ varied research endeavors. Launched in the spring of 2018, the Undergraduate Research Excellence Program (UREP) at Virginia Tech provides a programmatic pathway to assess student interest in collecting, organizing, and reflecting on their undergraduate research experiences. UREP is currently offered as a discipline agnostic and to provide multiple on-ramps into the program. The program has generated interest from students in every College and, to date, 608 students have enrolled. This presentation discusses results and metrics regarding the expansion, assessment, and program updates of UREP and will provide an adaptable framework, program model, and openly-accessible materials for directors/coordinators of undergraduate research offices or programs.
CyberBioSecurity through Leadership-as-Practice Development
Kaufman, Eric K.; Adeoye, Samson; Batarseh, Feras; Brown, Anne M.; Drape, Tiffany A.; Duncan, Susan; Rutherford, Tracy; Strawn, Laura K.; Xia, Kang (2022-03-28)
CyberBioSecurity is an emerging field at the interface of life sciences and digital worlds (Murch, 2018). The solution to the global cyberbiosecurity challenge is not merely technical; society needs cyberbiosecurity professionals who engage in leadership with a boundary-crossing approach that involves collective effort. Such an approach emerges from leadership-as-practice development (LaPD), characterized by its efforts to “change patterns and thinking that could transform a culture of mediocrity to one of excellence and resilience'' (Raelin, 2020, p. 2). While LaPD has been used in some professional learning contexts and it aligns with some signature pedagogies of the professions, the opportunity remains for embedding LaPD in graduate education to meet the needs of emerging fields. The objective of this proposed project is to catalyze transformative cyberbiosecurity graduate education in a way that increases cognitive integrative capability among cyberbiosecurity scientists and professionals. As noted by Pratch (2014), “leaders who possess integrative capacity are better able to assess problems and find workable solutions than those who do not” (p. 1). In this project, we intend to embedding LaPD in online graduate and train-the-trainer modules, testing various pedagogies associated with boundary-crossing graduate education. The approach will include use of collaborative leadership learning groups (CLLGs), which are “anchored in practice, bringing together learners who can identify and work together on the challenges they face collectively” (Denyer & Turnbull James, 2016, p. 269). Our specific research questions include: What signature pedagogies best support the emerging discipline of CyberBioSecurity education? To what extent do collaborative leadership learning groups (CLLGs) increase students’ cognitive integrative capability?
Cyberbiosecurity Workforce Preparation: Education at the Convergence of Cybersecurity and Biosecurity
Adeoye, Samson; Lindberg, Heather; Bagby, B.; Brown, Anne M.; Batarseh, Feras; Kaufman, Eric K. (2024-01)
Cyberbiosecurity is an emerging field at the convergence of life sciences and the digital world. As technological advances improve operational processes and expose them to vulnerabilities in agriculture and life sciences, cyberbiosecurity has become increasingly important for addressing contemporary concerns. Unfortunately, at this time, educational opportunities for cyberbiosecurity workforce preparation are limited. Stakeholders’ perceptions may help guide cyberbiosecurity workforce preparation efforts and bridge the gap from the classroom to the field. Toward this end, we identified stakeholders in education, private industry, and state agencies in [State] and sought their input through both an online survey and focus groups. Findings suggest limited awareness and understanding of cyberbiosecurity. Results indicate that both formal and non-formal learning components—including short modules and comprehensive standalone courses—are important for cyberbiosecurity education programming. Stakeholders tied potential success of education programming to systems thinking and collaborative designs. Moreover, results reveal insights into concerns at the convergence of information technology (IT) and operational technology (OT), which is central to effective workforce preparation for today’s agriculture and life sciences professionals. Continuous interdisciplinary collaboration and academia-industry partnerships will be critical for developing robust cyberbiosecurity education and securing the future of agriculture.
Defining Novel Clusters of PPAR gamma Partial Agonists for Virtual Screening
Collins, Erin Taylor (Virginia Tech, 2022-06-03)
Peroxisome proliferator-activated receptor γ (PPARγ) is associated with a wide range of diseases, including type 2 diabetes mellitus (T2D). Thiazolidinediones (TZDs) are agonists of PPARγ which have an insulin sensitizing effect, and are therefore used as a treatment for T2D. However, TZDs cause negative side effects in patients, such as weight gain, edema, and increased risk of bone fracture. Partial agonists could be an alternative to TZD-based drugs with fewer side effects. However, there is a lack of understanding of the types of PPARγ partial agonists and how they differ from full agonists. In silico techniques, like virtual screening, molecular docking, and pharmacophore modeling, allow us to determine and characterize markers of varying levels of agonism. An extensive search of the RCSB Protein Data Bank found 62 structures of PPARγ resolved with partial agonists. Cross-docking was performed and found that two PDB structures, 3TY0 and 5TWO, would be effective as receptor structures for virtual screening. By clustering known partial agonists by common pharmacophore features, we found several distinct groups of partial agonists. Interaction and pharmacophore models were created for each group of partial agonists. Virtual screening of FDA-approved compounds showed that the models were able to predict potential partial agonists of PPARγ. This study provides additional insight into the different binding modes of partial agonists of PPARγ and their characteristics. These models can be used to assist drug discovery efforts for intelligently designing novel therapeutics for T2D which have fewer negative side effects.
DESIGN THINKING for Visualizing Acid-Base Chemistry - Documenting a user-centered approach for designing and developing an ADA compliant online tool for visualizing acid-base chemistry
Stamper, Michael J.; Briganti, Jonathan; Brown, Anne M.; Dietrich, Andrea M.; Godrej, Adil N.; Schreiber, Madeline E.; Walz, Anita R. (2019-07-17)
This project created an online tool, that we call “The pkAnalyzer”. It enables the exploration of acid-conjugate base distributions in an easy to use Web interface. This project is also an example of the disciplines of Arts and Design into the STEM sciences, i.e. STEM to STEAM, and University Libraries commitment to faculty, students, and staff throughout the Virginia Tech system, in the areas of data visualization and design services to aid in the research process and communication of results. Beyond the functionality of the tool, this project involved the planning and designing a custom, modifiable, and attractive user interface (UI) and visualization that are "user-friendly", and incorporate the World Wide Web Consortium’s Web Content Accessibility Guidelines (WCAG), and falls with the Federal Governement’s Section 508 guidelines pertaining to creating and maintaining information and communications technology (ICT) that is accessible to people with disabilities relating to vision. Using a "Design Thinking" approach, all aspects of the design of this tool – User Interface (UI), User Experience (UX), Interaction Design (IxD), Graphic – were taken into account, and developed to enhance the user's experience using the tool, and undertanding of a complex chemical concept that is widely used in the basic and applied sciences and engineering.
Determining and Exploiting Common Interactions in the Peptidyl Transferase Center for Enhanced Derivative and Bidentate Design
Briganti, Anthony Joseph (Virginia Tech, 2024-05-29)
It is predicted that by 2050 there will be 10 million deaths annually due to super-resistant bacterial infections. Antimicrobial resistance (AMR) is already responsible for nearly 5 million deaths a year. Ribosomes serve as an ideal drug target being frequently targeted by antibiotics and having a highly conserved structure with few options for resistance. However, computer aided drug design (CADD) using ribosome crystal structures presents several challenges and is underutilized in the field. In this work we establish a successful protocol for antibiotic redocking and docking within the high interest sites of the peptidyl transferase center (PTC). Molecular visualization and interaction mapping were used to atomistically delineate binding patterns in the ribosomal PTC that could be used for CADD. Eleven ribosome crystal structures were validated for computational testing, which revealed derivative binding patterns in the A-site and P-site that can be used to increase antibiotic efficacy. Ribosome overlays revealed high interaction frequency nucleotides that were widely conserved throughout the different species and could be used to inform bidentate design to target two pockets at once. This work serves as a basis for methods to computationally explore drug optimization on ribosome targeting antibiotics to help combat the rapid expansion of AMR.
Development and Feasibility of an Online Brief Emotion Regulation Training (BERT) Program for Emerging Adults
Gatto, Alyssa Jo; Elliott, Truitt J.; Briganti, Jonathan S.; Stamper, Michael J.; Porter, Nathaniel D.; Brown, Anne M.; Harden, Samantha M.; Cooper, Lee D.; Dunsmore, Julie C. (Frontiers, 2022-06-10)
Mental wellness is a critical component of healthy development in emerging adulthood and serves to protect against stress and promote resilience against psychopathology. Emotion regulation is a key mechanism for effective prevention because of its role in socio-emotional competence and its transdiagnostic significance for psychopathology. In this feasibility study, a brief, time and cost-effective emotion regulation training program for emerging adults (BERT) was developed and tested using the RE-AIM framework. Importantly, building interventions within the context of an implementation framework, such as the RE-AIM framework, enhances the chances that an intervention will be able to scale out and scale up. First, the brainwriting premortem method was utilized to refine program content, conducting focus groups a priori to identify potential program failures prior to program implementation. Undergraduate students (n = 12) attended four focus groups presenting initial program content. Four clinicians were also interviewed to determine program barriers. Qualitative analyses aggregated participant feedback to identify compliments, changes, and concerns about BERT and critical feedback was immediately implemented prior to initial testing. BERT was rooted in cognitive-behavioral practices and informed by the Gross model of emotion regulation. The 5-week program was then examined in a college sample (N = 42) to evaluate implementation (low attrition, high content engagement, favorable attitudes, low incidence of technical errors, costs), reach (enrollment and completion demographics comparable to the population in which recruitment took place), and efficacy (positive change in emotion regulation pre- to post-program). Of the recruited participants, 36 remained in the study where 27 completed at least 80% of program content. Repeated-measures ANOVAs exhibited significant improvements in emotion regulation, psychological distress, and negative affectivity, suggesting promising initial efficacy. Initial data provide support for feasibility and a future randomized control trial. BERT has potential significance for promoting healthy development as its brief electronic format reduced barriers and the program development process incorporated stakeholder feedback at multiple levels to inform better implementation and dissemination.
Distinguishing our Undergraduate Researchers: Perspectives on an Innovative Campus-Wide Framework at Two R1 Land Grant Institutions
MacDonald, Amanda B.; Brown, Anne M.; Swaby, Keri; Ferstel, Sarah (2022-06-29)
There is an increasing need to relate cross-institutional strategies to elevate undergraduate research and foster collaborations. Many students participate in more than one research experience at their home institutions, and some will also have the opportunity to conduct research outside of their home institutions, such as at NSF REU sites, which allows them to engage with new faculty, content, and research. This creates a space for universities to celebrate all types of student research experiences, even research conducted at other institutions, and offer a programmatic structure that not only provides a roadmap for students in terms of participation but also a connector to key university resources. Here, two research-intensive, land-grant institutions discuss their innovative framework to aid launching UR tracking programs. The framework for these programs is highly adaptable and helps with development and implementation. In this presentation, speakers will discuss the varied research landscape for students across the two universities and challenges commonly faced by those in UR supporting roles, such as UR librarians and Directors of Offices of UR. They will provide an overview of their UR tracking programs and how this type of programmatic framework can assist in connecting with student researchers, offering essential training and support for both students and mentors, celebrating the success of students, and identifying the reach and impact the framework provides OURs and other support units, such as University Libraries. The speakers will showcase where their programs overlap and diverge, share cross-institutional strategies for learning and collaboration, and address how this framework allows for flexibility and adaptability. This type of UR programmatic approach not only benefits librarians and Directors but also students, mentors, and the undergraduate research community at large. A set curriculum for UR does not exist for every student, so this program structure offers goalposts for students, particularly those seeking to maximize their research participation potential while in college and/or their future careers in research. Faculty mentors and UR program directors can integrate any or all of the framework’s resources, training, and requirements to build their own recommended path for students. Attendees will leave this session with access to the programmatic framework alongside a “menu” of options for program development and growth, and access to other types of openly accessible UR resources. Following the session, attendees will be able to practice programmatic development using the menu, draft UR tracking programs that celebrate student success, and integrate any shared materials or the framework itself into usable programing at their home institutions.
Dynamics and Electrostatics of Membrane Proteins using Polarizable Molecular Dynamics Simulations
Montgomery, Julia Mae (Virginia Tech, 2024-06-25)
Membrane proteins are critical to many biological processes, including molecular transport, signal transduction, and cellular interactions. Through the use of molecular dynamics (MD) simulations, we are able to model this environment at an atomistic scale. However, traditionally used nonpolarizable force fields (FF) are thought to model the unique dielectric gradient posed by the lipid environment with a limited accuracy due to the mean field approximation of charge. Advancements in polarizable FFs and computing efficiency has enabled the explicit modeling of polarization responses and charge distribution, enabling a deeper understanding of the electrostatics driving these processes. Through the use of the Drude FF, we study three specific model systems to understand where explicit polarization is important in describing membranes and membrane proteins. These studies sought to answer the questions: (1) How does explicit electronic polarization impact small molecule permeation and localization preference?, (2) What electrostatic interactions underlie membrane protein secondary structure?, and (3) How do conformational changes propagate between microswitches in G-Protein Coupled Receptors? In this work, we show small molecule dipole moments changing as a function of localization in the bilayer. Additionally, we show differences in the free energy surfaces of permeation for aromatic, polar, and negatively charged species reliant upon force field used. For secondary structure, we showed key interactions which aided to stabilize model helices in bilayers. Finally, we showed potential inductive effects of key microswitch residues underlying prototypical G-Protein coupled receptor activation. This dissertation has helped to show the importance of including explicit polarization in membrane protein systems, especially when considering interactions at the interface and modeling species with charge. This work enables a refined view of the electrostatics occurring in membranes and membrane protein systems, and in the future, can be used as a basis for methodologies in computer aided drug design efforts.
Electrostatic properties at the interface of p53 Transactivation domain binding
Corrigan, Alexsandra Nikol (Virginia Tech, 2021-05-25)
Intrinsically disordered proteins (IDPs) are an abundant class of proteins and protein regions which rapidly change between multiple structures without an equilibrium position. IDPs exist as a series of conformational ensembles of semi-stable conformations that can be adopted based on a hilly landscape of shallow free energy minima. Disordered sequences share characteristic features differentiating them from globular proteins, including low sequence complexity, low occurrence of hydrophobic residues, high polar and charged residue content, and high flexibility. IDPs are commonly involved in regulation in the cell, and frequently function as, or interact with, hub proteins in protein-protein interaction networks, making them an important class of macromolecules for understanding regulatory and other processes. Given their functional importance, these proteins are widely studied. Many analytical techniques are used, though rapid conformational sampling by IDPs makes it difficult to detect many states with NMR or other techniques. Computational approaches such as molecular dynamics are increasingly used to probe the binding and conformational sampling of these proteins, allowing for observation of factors that cannot be observed with traditional analytical methods such as NMR, such as differing conformational ensembles and the dipoles of individual residues. Here, we studied the role of electrostatic interactions in IDP protein-protein interaction using molecular dynamics simulations performed with the Drude-2019 force field (FF), a polarizable model that allows for more accurate representation of electrostatics, an important factor for highly charged systems like IDPs. For this project, a prototypical protein with disordered regions, p53, was simulated with two protein partners, the nuclear coactivator domain of the CREB binding protein (CBP), and the E3 ubiquitin-protein ligase mouse double minute 2 (MDM2). p53 is widely studied, and the p53 transactivation domain (TAD) is disordered and binds to many structurally diverse partners, making this protein domain a useful model for probing the role of electrostatic interactions formed by IDPs at protein-protein binding interfaces. We found that the Drude-2019 FF allows for simulation of the p53 TAD with Cα chemical shifts comparable to those observed with NMR, supporting that the Drude-2019 FF performs well in simulating IDPs. We observed large relative change in sidechain dipole moments when comparing the p53 TAD alone and when bound to either CBP or MDM2. We observed that aliphatic and aromatic amino acids experienced the largest relative change in sidechain dipole moments, and that there is sensitivity to binding shown in this dipole response. The largest percent changes in sidechain dipole moment were found to localize at and around the binding interface. Understanding the binding interactions of IDPs at a fundamental level, including the role of electrostatic interactions, may help with targeting IDPs or their partners for drug design.
Enhancing Collaboration Across the Research Ecosystem: Using Libraries as Hubs for Discipline-Specific Data Experts
Ogier, Andrea; Brown, Anne M.; Petters, Jonathan L.; Hilal, Amr E.; Porter, Nathaniel D. (2018-07-24)
Computationally-intensive, cross-disciplinary research collaborations are difficult to create and maintain over time, though many yield impressive results. The need for researchers to share, maintain, and manage data is increasing, while also integrating new tools and approaches to make their work more impactful. The University Libraries at Virginia Tech has a team of disciplinary data and informatics consultants working to connect research environments on campus with emerging library services enabling collaboration across disciplines. Partnerships with university-level research service providers, such as high-performance computing (HPC) services and statistical data consulting, have presented interesting use cases and innovative solutions to common problems. While traditional library services may not overlap with high performance computing environments, new library services (such as data management, publishing, curation, archiving, and preservation) provide new avenues for collaboration and situate the libraries in a unique position in relation to research ecosystems. Moving large datasets from HPC environments into research environments present significant barriers to research data sharing between collaborators; working with libraries to make these datasets better organized and documented lowers some of these barriers. Discipline-specific informatics consulting allows researchers to integrate new tools and approaches to solve research questions. Here, we highlight the utilization, need, and scope of informatics and research data management services in and around libraries, while also providing examples of how these services have created new collaborations and adoption of improved research practices surrounding data management and integration of computationally intensive techniques (e.g. bioinformatics, humanistic informatics, etc.). This work lays the foundation for these services in an academic setting and the influence of such on the practice and experience of understanding data.
Exploring the Forces Underlying the Dynamics and Energetics of G-quadruplexes with Polarizable Molecular Dynamics Simulations
Salsbury, Alexa Marie (Virginia Tech, 2021-05-24)
G-quadruplexes (GQs) are highly stable noncanonical nucleic acid structures that form in the DNA of human cells and play fundamental roles in maintaining genomic stability and regulating gene expression. These unique structures exert broad influence over biologically important processes and can modulate cell survival and human health. In fact, mutations, hyper-stability, and dissociation of GQs are implicated in neurodegenerative disease, mental retardation, premature-aging conditions, and various cancers. As such, GQs are novel drug targets. GQ-targeting therapeutics are developed to influence the folding and genetic interactions of GQs that are implicated in diseased states. To do so requires a greater understanding of GQ structure and dynamics and molecular dynamics (MD) simulations are well suited to provide these fundamental insights. Previous MD simulations of GQs have provided limited information due to inaccuracies in their models, namely the nonpolarizable nature of their force fields (FFs). The cutting-edge Drude polarizable FF models electronic degrees of freedom, allowing charge distribution to change in response to its environment. This is an important component for modeling ion-ion and ion-DNA interactions and can influence the overall stability of GQ structures. The work herein employs the Drude polarizable FF to 1) describe the role of electronic structure on the dynamics and folded stability of GQs, 2) determine the impact of ion interaction on GQ stability, and 3) characterize the role of G-hairpin motifs in GQ intermediates. Such fundamental investigations will help clarify GQs role in healthy and diseased states and transform our understanding of noncanonical DNA, improving human health, therapeutic design, and fundamental science.
Finding What Is Inaccessible: Antimicrobial Resistance Language Use among the One Health Domains
Wind, Lauren L.; Briganti, Jonathan; Brown, Anne M.; Neher, Timothy P.; Davis, Meghan F.; Durso, Lisa M.; Spicer, Tanner; Lansing, Stephanie (MDPI, 2021-04-03)
The success of a One Health approach to combating antimicrobial resistance (AMR) requires effective data sharing across the three One Health domains (human, animal, and environment). To investigate if there are differences in language use across the One Health domains, we examined the peer-reviewed literature using a combination of text data mining and natural language processing techniques on 20,000 open-access articles related to AMR and One Health. Evaluating AMR key term frequency from the European PubMed Collection published between 1990 and 2019 showed distinct AMR language usage within each domain and incongruent language usage across domains, with significant differences in key term usage frequencies when articles were grouped by the One Health sub-specialties (2-way ANOVA; p < 0.001). Over the 29-year period, “antibiotic resistance” and “AR” were used 18 times more than “antimicrobial resistance” and “AMR”. The discord of language use across One Health potentially weakens the effectiveness of interdisciplinary research by creating accessibility issues for researchers using search engines. This research was the first to quantify this disparate language use within One Health, which inhibits collaboration and crosstalk between domains. We suggest the following for authors publishing AMR-related research within the One Health context: (1) increase title/abstract searchability by including both antimicrobial and antibiotic resistance related search terms; (2) include “One Health” in the title/abstract; and (3) prioritize open-access publication.
Flavin-dependent Enzymes in Natural Product Biosynthesis
Valentino, Hannah Rachel (Virginia Tech, 2021-03-31)
Natural products are biologically active metabolites produced by fungi, bacteria, and plants that have an extended application in pharmaceutical and chemical industries. Because of their chemical versatility, flavoenzymes are commonly involved in natural product biosynthetic pathways. This has given rise to the identification of flavoenzymes that are promising candidates for biomedical and biotechnical applications. This dissertation discusses the characterization of three flavoenzymes involved in natural product biosynthesis. The class B flavin-dependent monooxygenases S-monoooxygenase from Allium sativum (AsFMO) and N-hydroxylating monooxygenase from Streptomyces sp. XY332 (FzmM) were studied. Both enzymes perform heteroatom oxidation as part of allicin or fosfazinomycin biosynthesis respectively. AsFMO was predicted to oxidize S-allyl-L-cysteine (SAC) to alliin in allicin biosynthesis. Surprisingly, AsFMO exhibited negligible activity with SAC, and instead was highly active with allyl mercaptan and NADPH. This contradicted the initial proposal and suggested that AsFMO is involved in an alternative path producing allicin directly from allyl mercaptan. FzmM was identified to perform multiple N-oxidations which lead to the formation of a nitro group. FzmM performed a highly coupled and specific reaction with L-aspartate and NADPH to produce nitrosuccinate. Both AsFMO and FzmM followed a kinetic mechanism representative of class B flavin-dependent monooxygenases with a rapid pro-R stereospecific reduction and the formation of a C(4a)-hydroperoxyflavin intermediate during oxidation. In addition, the AsFMO structure was obtained and consisted of two domains for FAD and NADPH binding signature of class B monooxygenases. The biochemical and structural study of the Acinetobacter baumannii siderophore interacting protein (BauF) was also accomplished. This enzyme is essential in acinetobactin mediated iron assimilation and is important for virulence. The characterization of the binding and reduction of acinetobactin-ferric iron complex revealed that BauF is specific for this substrate and does not utilize NAD(P)H as an electron donor. The unique activity and structure of BauF can aid future drug design.
Fostering Communities of Transformation in STEM Higher Education: A Multi-institutional Collection of DEI Initiatives
Briganti, Jonathan S.; Sible, Jill C.; Brown, Anne M. (Virginia Tech Publishing, 2024-02-01)

Dive into the multifaceted landscape of inclusive excellence in STEM education with Fostering Communities of Transformation in STEM Higher Education. This scholarly work examines transformative initiatives from Virginia Tech, Radford University, Trinity Washington University, and Towson University, showcasing their role as catalysts in cultivating inclusive excellence across diverse STEM disciplines. Take inspiration from their projects and guidance from their lessons learned with this collection. Are you reviewing or adopting this book for a course?
Please help us understand your use by filling out this form. How to access this book
The main landing page for this book is https://doi.org/10.21061/fosteringcommunities.
The open textbook is freely available online in multiple formats including PDF and EPUB.
A paperback print version (in color) is available and can be ordered here. ISBNs
ISBN (PDF): 978-1-957213-84-2
ISBN (EPUB): 978-1-957213-83-5
ISBN (print): 978-1-957213-82-8
Table of contents 1. Preparing STEM Teachers to Be Change Makers 2. Resequencing the Chemistry Curriculum to Retain Chemistry Majors 3. Delayed Enrollment in General Chemistry Recitation 4. Assessing Changes in Student Engagement Using a Mixed-Methods Approach 5. Development and Assessment of a Four-Week Summer Research Experience for Undergraduates 6. Creating Impactful Moments 7. Community, Curriculum, and CUREs 8. We’re All in This Together
VIGNETTE: Reflecting on the Impact of Engelpalooza 9. Teaching to Make Math Resonate 10. Strategies for Creating and Sustaining Inclusive Makerspaces 11. Creating a Space in the Curriculum for Effective Mentoring to Foster Student Connections and Agency 12. Gunpowder Code Club 13. Using Departmental Book Clubs to Bridge the Faculty-Staff-Student Gap 14. Institutionally Advancing Inclusive Excellence 15. From the Soul
About the editors
Jonathan S. Briganti
Jonathan S. Briganti works in the Virginia Tech University Libraries as the manager of the DataBridge program, which trains undergraduate students from across all disciplines in applied data science and consults with partners across and beyond campus to improve the quality of their data and its outputs. He received both his BS and MS from Virginia Tech and has since found passion in creating open-source educational resources and accessible research environments to bring a more engaged and diverse pool of researchers to the table. Jill C. Sible
Jill C. Sible serves as Associate Vice Provost for Undergraduate Education and Professor of Biological Sciences at Virginia Tech where she has worked since 1998. She is the Program Director of Virginia Tech’s Inclusive Excellence project, which has empowered science faculty and departments to apply a learning mindset and data-informed approach to changing classes, curricula, and culture to be inclusive of all students, especially those historically marginalized in science and higher education. Anne M. Brown
Anne M. Brown is an Associate Professor and Associate Director in Research and Informatics under University Libraries, Virginia Tech and is an Affiliate Professor in the Biochemistry Department. As a computational biochemist, her research focuses on computer-aided drug discovery and the aggregation process of amyloids. She is committed to undergraduate research and outreach. Today, she continues in her lifelong mission to create and expand opportunities for students of all backgrounds and provide them with mentorship to facilitate their success. Suggested citation
Jonathan S. Briganti, Jill C. Sible, and Anne M. Brown, eds. (2024). Fostering Communities of Transformation in STEM Higher Education: A Multi-institutional Collection of DEI Initiatives. Blacksburg: Virginia Tech Publishing. https://doi.org/10.21061/fosteringcommunities. Licensed with CC BY 4.0. View errata | Report an error Accessibility
Virginia Tech is committed to making its publications accessible in accordance with the Americans with Disabilities Act of 1990. Please contact publishing@vt.edu if you are a person with a disability and have suggestions to make this book more accessible. Cover design: Catherine Freed

Browsing by Author "Brown, Anne M."

Results Per Page

Sort Options