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- ACE2 host receptor (3)
- Molecular dynamics (3)
- SARS-CoV-2 spike protein (3)
- Allosteric interactions (2)
- Mutational scanning (2)
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- Signal transmission (2)
- Air pollution (1)
- Allosteric binding pockets (1)
- Allosteric communication (1)
- Allosteric communications (1)
- Antibody escape (1)
- Binding energetics (1)
- Binding energy hotspots (1)
- Binding free energy (1)
- Binding hotspots (1)
- Biophysical methods (1)
- Brain aging (1)
- Climate change (1)
- Conformational dynamics (1)
- Depression (1)
- Disaster (1)
- Dynamic network modeling (1)
- Epistatic effects (1)
- Evacuation (1)
- Health (1)
- Human mobility (1)
- Mutational profiling (1)
- Mutational sensitivity (1)
- Nanobodies (1)
- Network analysis (1)
Articles 1 - 7 of 7
Full-Text Articles in Physical Sciences and Mathematics
Crisisready's Novel Framework For Transdisciplinary Translation: Case-Studies In Wildfire And Hurricane Response, Andrew Schroeder, Caleb Dresser, Akash Yadav, Jennifer Chan, Shenyue Jia, Caroline Buckee, Satchit Balsari
Crisisready's Novel Framework For Transdisciplinary Translation: Case-Studies In Wildfire And Hurricane Response, Andrew Schroeder, Caleb Dresser, Akash Yadav, Jennifer Chan, Shenyue Jia, Caroline Buckee, Satchit Balsari
Institute for ECHO Articles and Research
Extreme weather events including wildfires and hurricanes are becoming increasingly hazardous due to climate change, and often result in transient or permanent population displacements. Disaster-related disruptions in infrastructure, workforce, wages, and social networks can combine with population displacements to result in interruptions in health care access and prolonged impacts on morbidity and mortality. The data needed to make health systems and emergency management approaches more resilient to these hazards, and more responsive to the needs of affected populations, are sequestered in silos across private corporations and public agencies. In two case studies, we describe how our research team at CrisisReady …
Probing Mechanisms Of Binding And Allostery In The Sars-Cov-2 Spike Omicron Variant Complexes With The Host Receptor: Revealing Functional Roles Of The Binding Hotspots In Mediating Epistatic Effects And Communication With Allosteric Pockets, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan
Probing Mechanisms Of Binding And Allostery In The Sars-Cov-2 Spike Omicron Variant Complexes With The Host Receptor: Revealing Functional Roles Of The Binding Hotspots In Mediating Epistatic Effects And Communication With Allosteric Pockets, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan
Mathematics, Physics, and Computer Science Faculty Articles and Research
In this study, we performed all-atom MD simulations of RBD–ACE2 complexes for BA.1, BA.1.1, BA.2, and BA.3 Omicron subvariants, conducted a systematic mutational scanning of the RBD–ACE2 binding interfaces and analysis of electrostatic effects. The binding free energy computations of the Omicron RBD–ACE2 complexes and comprehensive examination of the electrostatic interactions quantify the driving forces of binding and provide new insights into energetic mechanisms underlying evolutionary differences between Omicron variants. A systematic mutational scanning of the RBD residues determines the protein stability centers and binding energy hotpots in the Omicron RBD–ACE2 complexes. By employing the ensemble-based global network analysis, we …
Integrating Conformational Dynamics And Perturbation-Based Network Modeling For Mutational Profiling Of Binding And Allostery In The Sars-Cov-2 Spike Variant Complexes With Antibodies: Balancing Local And Global Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan
Integrating Conformational Dynamics And Perturbation-Based Network Modeling For Mutational Profiling Of Binding And Allostery In The Sars-Cov-2 Spike Variant Complexes With Antibodies: Balancing Local And Global Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan
Mathematics, Physics, and Computer Science Faculty Articles and Research
n this study, we combined all-atom MD simulations, the ensemble-based mutational scanning of protein stability and binding, and perturbation-based network profiling of allosteric interactions in the SARS-CoV-2 spike complexes with a panel of cross-reactive and ultra-potent single antibodies (B1-182.1 and A23-58.1) as well as antibody combinations (A19-61.1/B1-182.1 and A19-46.1/B1-182.1). Using this approach, we quantify the local and global effects of mutations in the complexes, identify protein stability centers, characterize binding energy hotspots, and predict the allosteric control points of long-range interactions and communications. Conformational dynamics and distance fluctuation analysis revealed the antibody-specific signatures of protein stability and flexibility of the …
Biophysical Insight Into The Sars-Cov2 Spike–Ace2 Interaction And Its Modulation By Hepcidin Through A Multifaceted Computational Approach, Hamid Hadi-Alijanvand, Luisa Di Paola, Guang Hu, David M. Leitner, Gennady M. Verkhivker, Peixin Sun, Humanath Poudel, Alessandro Giuliani
Biophysical Insight Into The Sars-Cov2 Spike–Ace2 Interaction And Its Modulation By Hepcidin Through A Multifaceted Computational Approach, Hamid Hadi-Alijanvand, Luisa Di Paola, Guang Hu, David M. Leitner, Gennady M. Verkhivker, Peixin Sun, Humanath Poudel, Alessandro Giuliani
Mathematics, Physics, and Computer Science Faculty Articles and Research
At the center of the SARS-CoV2 infection, the spike protein and its interaction with the human receptor ACE2 play a central role in the molecular machinery of SARS-CoV2 infection of human cells. Vaccine therapies are a valuable barrier to the worst effects of the virus and to its diffusion, but the need of purposed drugs is emerging as a core target of the fight against COVID19. In this respect, the repurposing of drugs has already led to discovery of drugs thought to reduce the effects of the cytokine storm, but still a drug targeting the spike protein, in the infection …
Structural And Computational Studies Of The Sars-Cov-2 Spike Protein Binding Mechanisms With Nanobodies: From Structure And Dynamics To Avidity-Driven Nanobody Engineering, Gennady M. Verkhivker
Structural And Computational Studies Of The Sars-Cov-2 Spike Protein Binding Mechanisms With Nanobodies: From Structure And Dynamics To Avidity-Driven Nanobody Engineering, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
Nanobodies provide important advantages over traditional antibodies, including their smaller size and robust biochemical properties such as high thermal stability, high solubility, and the ability to be bioengineered into novel multivalent, multi-specific, and high-affinity molecules, making them a class of emerging powerful therapies against SARS-CoV-2. Recent research efforts on the design, protein engineering, and structure-functional characterization of nanobodies and their binding with SARS-CoV-2 S proteins reflected a growing realization that nanobody combinations can exploit distinct binding epitopes and leverage the intrinsic plasticity of the conformational landscape for the SARS-CoV-2 S protein to produce efficient neutralizing and mutation resistant characteristics. Structural …
Allosteric Determinants Of The Sars-Cov-2 Spike Protein Binding With Nanobodies: Examining Mechanisms Of Mutational Escape And Sensitivity Of The Omicron Variant, Gennady M. Verkhivker
Allosteric Determinants Of The Sars-Cov-2 Spike Protein Binding With Nanobodies: Examining Mechanisms Of Mutational Escape And Sensitivity Of The Omicron Variant, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against the SARS-CoV-2 virus and resilience against mutational escape. In this study, we performed a comprehensive computational analysis of the SARS-CoV-2 spike trimer complexes with single nanobodies Nb6, VHH E, and complex with VHH E/VHH V nanobody combination. We combined coarse-grained and all-atom molecular simulations and collective dynamics analysis with binding free energy scanning, perturbation-response scanning, and network centrality analysis to examine mechanisms of nanobody-induced allosteric modulation and cooperativity in the SARS-CoV-2 spike trimer complexes with these nanobodies. By quantifying energetic and allosteric …
Ambient Air Pollution Exposure And Increasing Depressive Symptoms In Older Women: The Mediating Role Of The Prefrontal Cortex And Insula, Andrew J. Petkus, Susan M. Resnick, Xinhui Wang, Daniel P. Beavers, Mark A. Espeland, Margaret Gatz, Tara Gruenewald, Joshua Millstein, Helena C. Chui, Joel D. Kaufman, Joann E. Manson, Gregory A. Wellenius, Eric A. Whitsel, Keith Widaman, Diana Younan, Jiu-Chiuan Chen
Ambient Air Pollution Exposure And Increasing Depressive Symptoms In Older Women: The Mediating Role Of The Prefrontal Cortex And Insula, Andrew J. Petkus, Susan M. Resnick, Xinhui Wang, Daniel P. Beavers, Mark A. Espeland, Margaret Gatz, Tara Gruenewald, Joshua Millstein, Helena C. Chui, Joel D. Kaufman, Joann E. Manson, Gregory A. Wellenius, Eric A. Whitsel, Keith Widaman, Diana Younan, Jiu-Chiuan Chen
Psychology Faculty Articles and Research
Exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) have been associated with the emergence of depressive symptoms in older adulthood, although most studies used cross-sectional outcome measures. Elucidating the brain structures mediating the adverse effects can strengthen the causal role between air pollution and increasing depressive symptoms. We evaluated whether smaller volumes of brain structures implicated in late-life depression mediate associations between ambient air pollution exposure and changes in depressive symptoms. This prospective study included 764 community-dwelling older women (aged 81.6 ± 3.6 in 2008–2010) from the Women's Health Initiative Memory Study (WHIMS) Magnetic …