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Exploring Binding Pockets in the Conformational States of the SARS-CoV-2 Spike Trimers for the Screening of Allosteric Inhibitors Using Molecular Simulations and Ensemble-Based Ligand Docking
Get PDFUnderstanding mechanisms of allosteric regulation remains elusive for the SARS-CoV-2 spike protein, despite the increasing interest and effort in discovering allosteric inhibitors of the viral activity and interactions with the host receptor ACE2. The challenges of discovering allosteric modulators of the SARS-CoV-2 spike proteins are associated with the diversity of cryptic allosteric sites and complex molecular mechanisms that can be employed by allosteric ligands, including the alteration of the conformational equilibrium of spike protein and preferential stabilization of specific functional states. In the current study, we combine conformational dynamics analysis of distinct forms of the full-length spike protein trimers and machine-learning-based binding pocket detection with the ensemble-based ligand docking and binding free energy analysis to characterize the potential allosteric binding sites and determine structural and energetic determinants of allosteric inhibition for a series of experimentally validated allosteric molecules. The results demonstrate a good agreement between computational and experimental binding affinities, providing support to the predicted binding modes and suggesting key interactions formed by the allosteric ligands to elicit the experimentally observed inhibition. We establish structural and energetic determinants of allosteric binding for the experimentally known allosteric molecules, indicating a potential mechanism of allosteric modulation by targeting the hinges of the inter-protomer movements and blocking conformational changes between the closed and open spike trimer forms. The results of this study demonstrate that combining ensemble-based ligand docking with conformational states of spike protein and rigorous binding energy analysis enables robust characterization of the ligand binding modes, the identification of allosteric binding hotspots, and the prediction of binding affinities for validated allosteric modulators, which is consistent with the experimental data. This study suggested that the conformational adaptability of the protein allosteric sites and the diversity of ligand bound conformations are both in play to enable efficient targeting of allosteric binding sites and interfere with the conformational changes
Highlighting Health and Diversity: Curating Digital Exhibits to Promote Online Resources Across Cultural Months
Get PDFThis poster presentation demonstrates how digital exhibits can be leveraged to promote health literacy and enhance health education by creating awareness of resources to benefit diverse cultural and ethnic groups. It showcases examples of online exhibits that highlight health-related information, history, and resources to address health disparities and promote health equity among different populations
The Role of Positive Affect in Asthma Control and Symptom Severity in Adolescents
Get PDFIntroduction
We test the effects of positive affect and its arousal subscale components of calm, wellbeing, and vigor on asthma control and symptom severity in adolescents with moderate to severe asthma. Additionally, we test whether positive affect (and its arousal components) moderate how stress impacts asthma control and symptom severity. Methods
Adolescents with asthma (N = 66, ages 12–17) completed brief surveys 4 times a day for 7 days reporting on their positive affect, stress, and asthma symptom severity and conducted a morning peak expiratory flow assessment each day. Asthma control and psychological asthma triggers were assessed at the end of the 7 days. Results
Positive affect moderated the association between stress and asthma control (b = −0.33, p = 0.009) as well as the association between psychological triggers and asthma control (b = −0.74, p = 0.007). When assessing the positive affect arousal components, calm and wellbeing seemed to be driving these effects. Additionally, calm moderated the association between stress and asthma symptom severity (b = −0.33, p = 0.036) as well as the association between psychological triggers and asthma symptom severity (b = −0.75, p = 0.021). Conclusions
When considering patient stress (e.g., general stress, psychological asthma triggers), positive affect and its arousal components of calm and wellbeing may be helpful for patients with higher levels of stress and/or for patients experiencing greater numbers of psychological triggers
New Ways of Being White: White Families Striving to Raise Young Antiracists
Get PDFIn asking the questions “How are white families striving to create antiracist family cultures simultaneously resisting reifying white dominant culture, and how are white children making sense of their racial identities in those families?” I had the opportunity to deepen previously established relationships with three families asking similar questions. Our collective querying resulted in data collected using critical ethnographic methods rooted in culturally responsive methods including fieldwork, formal and informal conversations, and written narrative. Unique themes emerged from each family’s data, from which I drew three major theoretical conclusions: the importance of (1) Critical Consciousness (2) Antiracist Community, and (3) Unfinishedness. The data indicates the need for continued research regarding white children’s antiracist racial identity development in the social, familial, and schooling spheres, as well as the motivations that undergird white caregivers to attempt to act in antiracist ways. This study contributes to a current gap in the literature regarding the development of antiracist attitudes among white children
The Bicomplex Tensor Product and a Bicomplex Choi Theorem
Get PDFIn this paper we extend the concept of tensor product to the bicomplex case and use it to prove the bicomplex counterpart of the classical Choi theorem in the theory of complex matrices and operators. The concept of hyperbolic tensor product is also discussed, and we link these results to the theory of quantum channels in the bicomplex and hyperbolic case
q-rational Functions and Interpolation with Complete Nevanlinna–Pick Kernels
Get PDFIn this paper we introduce the concept of matrix-valued q-rational functions. In comparison to the classical case, we give different characterizations with principal emphasis on realizations and discuss algebraic manipulations. We also study the concept of Schur multipliers and complete Nevanlinna–Pick kernels in the context of q-deformed reproducing kernel Hilbert spaces and provide first applications in terms of an interpolation problem using Schur multipliers and complete Nevanlinna–Pick kernels
