4.7 Article

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

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Summary: Understanding the structure of how antibodies bind SARS-CoV-2 at an atomic level is crucial for developing more effective treatments for Covid-19. Using simulations, it was found that CR3022 has a higher affinity for the virus than 4A8, with electrostatic interactions playing a key role in this difference. This could guide the development of new antibodies with charged amino acids for combating Covid-19.

JOURNAL OF PHYSICAL CHEMISTRY B (2021)

Article Chemistry, Multidisciplinary

Free Energy Landscapes from SARS-CoV-2 Spike Glycoprotein Simulations Suggest that RBD Opening Can Be Modulated via Interactions in an Allosteric Pocket

Lucy Fallon et al.

Summary: The SARS-CoV-2 coronavirus spike protein plays a crucial role in viral entry and is a target for neutralizing antibodies. By using simulations, interactions influencing spike protein dynamics can be identified for potential therapeutic targeting. Small molecules binding to specific pockets may modulate the spike protein equilibrium and shed light on its conformational changes.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

Article Multidisciplinary Sciences

Broad sarbecovirus neutralization by a human monoclonal antibody

M. Alejandra Tortorici et al.

Summary: The emergence of SARS-CoV-2 variants and recurrent spillovers of coronaviruses into the human population emphasize the need for broadly neutralizing antibodies to prevent future zoonotic infections. The human monoclonal antibody S2X259 has shown promising results in neutralizing various forms of SARS-CoV-2 and potentially zoonotic sarbecoviruses by inhibiting the binding of ACE2 to the receptor-binding domain. This antibody targets a key antigenic site and may guide the design of vaccines effective against all sarbecoviruses.

NATURE (2021)

Article Chemistry, Multidisciplinary

SARS-CoV-2 simulations go exascale to predict dramatic spike opening and cryptic pockets across the proteome

Maxwell Zimmerman et al.

Summary: Researchers utilized the Folding@home project to simulate the viral proteome of SARS-CoV-2 and discovered 'cryptic' epitopes, with spike variants affecting the balance between receptor binding and immune evasion. The data and models generated provide valuable insight for the design of antiviral drugs.

NATURE CHEMISTRY (2021)

Article Chemistry, Multidisciplinary

A glycan gate controls opening of the SARS-CoV-2 spike protein

Terra Sztain et al.

Summary: Through simulations, the study reveals the mechanism of spike protein receptor binding domain (RBD) opening in SARS-CoV-2 infection, highlighting the crucial role of N-glycan in facilitating RBD opening. This research represents a milestone in ensemble pathway simulations and provides a foundation for understanding the fundamental mechanisms of viral entry and infection.

NATURE CHEMISTRY (2021)

Article Multidisciplinary Sciences

Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants

Lingshu Wang et al.

Summary: The study identified four receptor binding domain-targeting antibodies with potent neutralizing activity against 23 variants, including two ultrapotent antibodies. Combinations of these antibodies reduced the in vitro generation of escape mutants, showing potential in mitigating resistance development.

SCIENCE (2021)

Article Multidisciplinary Sciences

Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study

Kathryn M. Hastie et al.

Summary: Antibody-based therapeutics and vaccines are crucial in combating COVID-19, especially with mutations and transmission of SARS-CoV-2. An international consortium identified multiple RBD-directed antibody communities, providing a framework for selecting treatment cocktails.

SCIENCE (2021)

Article Microbiology

Signatures in SARS-CoV-2 spike protein conferring escape to neutralizing antibodies

Marta Alenquer et al.

Summary: Understanding the evolution of SARS-CoV-2 and host immunity is crucial in controlling COVID-19 pandemics. Mutations in the spike protein can impact antibody and ACE2 binding, requiring monitoring of SARS-CoV-2 evolution and dynamics. Identifying signatures in SARS-CoV-2 that make the virus resistant to neutralizing antibodies is critical for the development of therapies, vaccines, and diagnostics.

PLOS PATHOGENS (2021)

Article Biology

Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics

Michael Barton et al.

Summary: The study analyzed the effects of mutations in the Spike protein of SARS-CoV-2 on its interaction with ACE2, finding that most mutations increased affinity with ACE2. Two ACE2 mutations were also found to enhance binding with the Spike protein.

ELIFE (2021)

Article Microbiology

Comprehensive Deep Mutational Scanning Reveals the Immune-Escaping Hotspots of SARS-CoV-2 Receptor-Binding Domain Targeting Neutralizing Antibodies

Keng-Chang Tsai et al.

Summary: This study comprehensively investigated the mutational effects of RBD of SARS-CoV-2 on binding to neutralizing antibodies and ACE2. It identified certain residues consistent with clinically emerging variants or experimental observations. Common hotspots were also revealed to have comparable destabilizing effects on binding to both ACE2 and neutralizing antibodies.

FRONTIERS IN MICROBIOLOGY (2021)

Article Immunology

Epitope Classification and RBD Binding Properties of Neutralizing Antibodies Against SARS-CoV-2 Variants of Concern

Ashlesha Deshpande et al.

Summary: This study investigated the impact of RBD mutations in SARS-CoV-2 on ACE2 and NAb binding, revealing that mutations such as K417T, E484K, and N501Y disrupted the binding of 65% of evaluated NAbs, indicating concern for the P.1 Japan/Brazil strain. Additionally, the L452R mutation enhanced ACE2 binding affinity while disrupting C1 and C2 NAb classes.

FRONTIERS IN IMMUNOLOGY (2021)

Article Immunology

Rapid Increase in SARS-CoV-2 P.1 Lineage Leading to Codominance with B.1.1.7 Lineage, British Columbia, Canada, January-April 2021

Catherine A. Hogan et al.

Summary: This study evaluated the relative contribution of VOCs in nearly 67,000 infections in British Columbia during the first 16 weeks of 2021, finding that B.1.1.7, B.1.351, and P.1 showed different spreading patterns in the region. While B.1.1.7 and P.1 increased in proportion, P.1 expanded rapidly, while B.1.351 remained a minority.

EMERGING INFECTIOUS DISEASES (2021)

Article Multidisciplinary Sciences

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Daniel Wrapp et al.

SCIENCE (2020)

Article Biochemistry & Molecular Biology

Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2

Qihui Wang et al.

Article Biochemistry & Molecular Biology

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Alexandra C. Walls et al.

Article Multidisciplinary Sciences

Cross-neutralization ofSARS-CoV-2 by a human monoclonal SARS-CoV antibody

Dora Pinto et al.

NATURE (2020)

Article Biochemistry & Molecular Biology

Controlling the SARS-CoV-2 spike glycoprotein conformation

Rory Henderson et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2020)

Article Biochemistry & Molecular Biology

A thermostable, closed SARS-CoV-2 spike protein trimer

Xiaoli Xiong et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2020)

Article Biochemistry & Molecular Biology

Structure-guided covalent stabilization of coronavirus spike glycoprotein trimers in the closed conformation

Matthew McCallum et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2020)

Article Multidisciplinary Sciences

Structure-based design of prefusion-stabilized SARS-CoV-2 spikes

Ching-Lin Hsieh et al.

SCIENCE (2020)

Article Multidisciplinary Sciences

Distinct conformational states of SARS-CoV-2 spike protein

Yongfei Cai et al.

SCIENCE (2020)

Article Biochemical Research Methods

Molecular Simulations and Network Modeling Reveal an Allosteric Signaling in the SARS-CoV-2 Spike Proteins

Gennady M. Verkhivker

JOURNAL OF PROTEOME RESEARCH (2020)

Article Multidisciplinary Sciences

Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion

Donald J. Benton et al.

NATURE (2020)

Article Multidisciplinary Sciences

Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms

M. Alejandra Tortorici et al.

SCIENCE (2020)

Article Chemistry, Multidisciplinary

Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein

Lorenzo Casalino et al.

ACS CENTRAL SCIENCE (2020)

Article Microbiology

Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles

Maolin Lu et al.

CELL HOST & MICROBE (2020)

Article Multidisciplinary Sciences

SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo

Yixuan J. Hou et al.

SCIENCE (2020)

Article Chemistry, Medicinal

VMD Store-A VMD Plugin to Browse, Discover, and Install VMD Extensions

Henrique S. Fernandes et al.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2019)

Article Biochemical Research Methods

CHARMM36m: an improved force field for folded and intrinsically disordered proteins

Jing Huang et al.

NATURE METHODS (2017)

Article Biochemistry & Molecular Biology

The RCSB protein data bank: integrative view of protein, gene and 3D structural information

Peter W. Rose et al.

NUCLEIC ACIDS RESEARCH (2017)

Editorial Material Infectious Diseases

GISAID: Global initiative on sharing all influenza data - from vision to reality

Yuelong Shu et al.

EUROSURVEILLANCE (2017)

Article Chemistry, Physical

A Stochastic Algorithm for the Isobaric-Isothermal Ensemble with Ewald Summations for All Long Range Forces

Michele Di Pierro et al.

JOURNAL OF CHEMICAL THEORY AND COMPUTATION (2015)

Article Biochemistry & Molecular Biology

BeAtMuSiC: prediction of changes in protein-protein binding affinity on mutations

Yves Dehouck et al.

NUCLEIC ACIDS RESEARCH (2013)

Article Chemistry, Multidisciplinary

Frontier Residues Lining Globin Internal Cavities Present Specific Mechanical Properties

Anthony Bocahut et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2011)

Article Biochemistry & Molecular Biology

The FALC-Loop web server for protein loop modeling

Junsu Ko et al.

NUCLEIC ACIDS RESEARCH (2011)

Article Biophysics

Interaction Energy Based Protein Structure Networks

M. S. Vijayabaskar et al.

BIOPHYSICAL JOURNAL (2010)

Article Biochemistry & Molecular Biology

WIWS: a protein structure bioinformatics Web service collection

M. L. Hekkelman et al.

NUCLEIC ACIDS RESEARCH (2010)

Article Chemistry, Physical

Langevin thermostat for rigid body dynamics

Ruslan L. Davidchack et al.

JOURNAL OF CHEMICAL PHYSICS (2009)

Article Multidisciplinary Sciences

Dynamical networks in tRNA: protein complexes

Anurag Sethi et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

Article Biochemistry & Molecular Biology

Improved prediction of protein side-chain conformations with SCWRL4

Georgii G. Krivov et al.

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS (2009)

Article Biochemistry & Molecular Biology

Locating the active sites of enzymes using mechanical properties

Sophie Sacquin-Mora et al.

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS (2007)

Article Biochemistry & Molecular Biology

ArchPRED: a template based loop structure prediction server

Narcis Fernandez-Fuentes et al.

NUCLEIC ACIDS RESEARCH (2006)

Article Biophysics

Investigating the local flexibility of functional residues in hemoproteins

S Sacquin-Mora et al.

BIOPHYSICAL JOURNAL (2006)

Article Biophysics

A new generation of statistical potentials for proteins

Y Dehouck et al.

BIOPHYSICAL JOURNAL (2006)

Article Biochemistry & Molecular Biology

Residues crucial for maintaining short paths in network communication mediate signaling in proteins

Antonio del Sol et al.

MOLECULAR SYSTEMS BIOLOGY (2006)

Review Chemistry, Multidisciplinary

Scalable molecular dynamics with NAMD

JC Phillips et al.

JOURNAL OF COMPUTATIONAL CHEMISTRY (2005)

Article Biochemical Research Methods

ModLoop: automated modeling of loops in protein structures

A Fiser et al.

BIOINFORMATICS (2003)