From viral assembly to host interaction: AFM’s contributions to virology DOI Creative Commons
Ankita Ray, Joshua D. Simpson,

Irem Demir

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: 99(1)

Published: Dec. 10, 2024

Viruses represent a diverse pool of obligate parasites that infect virtually every known organism, as such, their study is incredibly valuable for range fields including public health, medicine, agriculture, and ecology, the development biomedical technologies. Having evolved over millions years, each virus has unique often complicated biology, must be characterized on case-by-case basis, even between strains same taxon. Owing to its nanoscale spatial resolution, atomic force microscopy (AFM) represents powerful tool exploring structural features, kinetics binding host cell ligands, virion self-assembly, budding behaviors. Through availability numerous chemistries advances in imaging modes, AFM able explore complex web host-virus interactions life-cycle at single level, features level individual bonds molecules. Due wide array techniques developed data analysis approaches available, can provide information cannot furnished by other modalities, especially level. Here, we highlight methods obtained through use AFM, demonstrating both utility versatility viruses. As technology continues rapidly evolve, likely remain an integral part research, providing important insight into many aspects virology.

Language: Английский

GōMartini 3: From large conformational changes in proteins to environmental bias corrections DOI Creative Commons
Paulo C. T. Souza, Luís Borges-Araújo,

Chris Brasnett

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 16, 2024

ABSTRACT Coarse-grained modeling has become an important tool to supplement experimental measurements, allowing access spatio-temporal scales beyond all-atom based approaches. The GōMartini model combines structure- and physics-based coarse-grained approaches, balancing computational efficiency accurate representation of protein dynamics with the capabilities studying proteins in different biological environments. This paper introduces enhanced model, which a virtual-site implementation Gō models Martini 3. been extensively tested by community since release new version Martini. work demonstrates diverse case studies, ranging from protein-membrane binding protein-ligand interactions AFM force profile calculations. is also versatile, as it can address recent inaccuracies reported model. Lastly, discusses advantages, limitations, future perspectives 3 its combination models.

Language: Английский

Citations

22
Molecular Determinants for the Binding of the Highly Infectious SARS-CoV-2 Omicron (BA.1) Variant to the Human ACE2 Receptor DOI Creative Commons

Majed S. Aljohani,

Pawan Bhatta,

Xiche Hu

et al.

Physchem, Journal Year: 2025, Volume and Issue: 5(1), P. 8 - 8

Published: Feb. 20, 2025

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continually undergoes mutation, leading to variants with altered pathogenicity and transmissibility. The Omicron variant (B.1.1.529), first identified in South Africa 2021, has become dominant strain worldwide. It harbors approximately 50 mutations compared original strain, 15 located receptor-binding domain (RBD) spike protein that facilitates viral entry via binding human angiotensin-converting enzyme (ACE2) receptor. How do these mutated residues modulate intermolecular interactions affinity between RBD ACE2? This is a question great theoretical importance practical implication. In this study, we employed quantum chemical calculations at B2PLYP-D3/def2-TZVP level theory investigate molecular determinants governing Omicron’s ACE2 interaction. Comparative analysis wild-type RBD–ACE2 interfaces revealed including S477N, Q493R, Q498R, N501Y enhance through formation bifurcated hydrogen bonds, π–π stacking, cation–π interactions. These favorable counterbalance such destabilizing as K417N, G446S, G496S, Y505H, which disrupt salt bridges bonds. Additionally, allosteric effects improve contributions non-mutated (notably A475, Y453, F486) structural realignment novel bonding S19, an overall increase electrostatic π-system interaction energy. conclusion, our findings provide mechanistic basis for increased infectivity offer valuable insights development targeted antiviral therapies. Moreover, from methodological perspective, directly calculated mutation-induced energy changes residue using advanced methods rather than relying on indirect decomposition schemes typical dynamics-based free analyses. strong correlation differences experimental deep mutational scanning (DMS) data underscores robustness framework predicting affinity. demonstrates potential predictive tools studying protein–protein guiding rational therapeutic design.

Language: Английский

Citations

1
GōMartini 3: From large conformational changes in proteins to environmental bias corrections DOI Creative Commons
Paulo C. T. Souza, Luís Borges-Araújo, Christopher Brasnett

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 30, 2025

Coarse-grained modeling has become an important tool to supplement experimental measurements, allowing access spatio-temporal scales beyond all-atom based approaches. The GōMartini model combines structure- and physics-based coarse-grained approaches, balancing computational efficiency accurate representation of protein dynamics with the capabilities studying proteins in different biological environments. This paper introduces enhanced model, which a virtual-site implementation Gō models Martini 3. been extensively tested by community since release reparametrized version Martini. work demonstrates diverse case studies, ranging from protein-membrane binding protein-ligand interactions AFM force profile calculations. is also versatile, as it can address recent inaccuracies reported model. Lastly, discusses advantages, limitations, future perspectives 3 its combination models.

Language: Английский

Citations

1
Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy DOI Creative Commons
Qingrong Zhang, Ricardo de Souza Rosa, Ankita Ray

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Abstract The SARS-CoV-2 spike protein’s membrane-binding domain bridges the viral and host cell membrane, a critical step in triggering membrane fusion. Here, we investigate how protein interacts with membranes, focusing on peptide (MBP) located near TMPRSS2 cleavage site. Through vitro computational studies, examine both primed (TMPRSS2-cleaved) unprimed versions of MBP, as well influence its conserved disulfide bridge binding. Our results show that MBP preferentially associates cholesterol-rich find cholesterol depletion significantly reduces infectivity. Furthermore, observe stabilizes MBP’s interaction suggesting structural role entry. Together, these findings highlight importance composition structure infectivity suggest targeting could provide therapeutic strategy against infection.

Language: Английский

Citations

0
Conformational and Stability Analysis of SARS-CoV-2 Spike Protein Variants by Molecular Simulation DOI Creative Commons
Gustavo E. Olivos-Ramírez, Luis Fernando Cofas‐Vargas, Tobias Madl

et al.

Pathogens, Journal Year: 2025, Volume and Issue: 14(3), P. 274 - 274

Published: March 12, 2025

We performed a comprehensive structural analysis of the conformational space several spike (S) protein variants using molecular dynamics (MD) simulations. Specifically, we examined four well-known (Delta, BA.1, XBB.1.5, and JN.1) alongside wild-type (WT) form SARS-CoV-2. The states each variant were characterized by analyzing their distributions within selected collective variables (CVs), such as inter-domain distances between receptor-binding domain (RBD) N-terminal (NTD). Our primary focus was to identify relevant potential transitions determine set native contacts (NCs) that stabilize these conformations. results reveal genetically more distant variants, JN.1, tend adopt compact compared WT. Additionally, exhibit novel NC profiles, an increased number specific distributed among ionic, polar, nonpolar residues. further analyzed impact mutations, including T478K, N500Y, Y504H. These mutations not only enhance interactions with human host receptor but also alter inter-chain stability introducing additional NCs Consequently, may influence accessibility certain regions neutralizing antibodies. Overall, findings contribute deeper understanding functional variations S variants.

Language: Английский

Citations

0
Probing living cell dynamics and molecular interactions using atomic force microscopy DOI
David Alsteens

Biophysical Reviews, Journal Year: 2024, Volume and Issue: 16(6), P. 663 - 677

Published: Dec. 1, 2024

Language: Английский

Citations

3
Nanomechanical footprint of SARS-CoV-2 variants in complex with a potent nanobody by molecular simulations DOI Creative Commons
Luis Fernando Cofas‐Vargas, Gustavo E. Olivos-Ramírez, Mateusz Chwastyk

et al.

Nanoscale, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Molecular dynamics simulations revealed variations in mechanostability among different SARS-CoV-2 variants complex with the H11-H4 nanobody.

Language: Английский

Citations

2
Redirecting a Broad-Spectrum Nanobody Against the Receptor-Binding Domain of SARS-CoV-2 to Target Omicron Variants DOI Creative Commons
Kwanpet Intasurat, Nonth Submunkongtawee,

Phoomintara Longsompurana

et al.

Applied Sciences, Journal Year: 2024, Volume and Issue: 14(22), P. 10548 - 10548

Published: Nov. 15, 2024

The urgent need for an effective COVID-19 therapy has propelled the exploration of innovative strategies to combat fast-mutating SARS-CoV-2 virus. This study attempted develop nanobodies (Nbs) against Omicron variants by redirecting 1.29 neutralizing Nb, a receptor-binding domain (RBD)-specific Nb that can protect various other than Omicron, target subvariant BA.5, variant used development bivalent vaccine. Error-prone libraries were constructed. Following two rounds selection using functional ligand-binding identification Tat-based recognition associating proteins (FLI-TRAP) technique, we rapidly identified Nbs, namely, C11 and K9, could RBD XBB.1.5, XBB.1.16 subvariants. Molecular docking provided insights into how these Nbs interact with BA.5 JN.1 variants. application directed evolution via utilization error-prone PCR synthetic E. coli applied in FLI-TRAP method may be powerful tool facilitating simple, fast economical redirect existing antibodies generate antibody fragments susceptible autonomous mutation, not only viral infection but also diseases, such as cancer.

Language: Английский

Citations

1
From viral assembly to host interaction: AFM’s contributions to virology DOI Creative Commons
Ankita Ray, Joshua D. Simpson,

Irem Demir

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: 99(1)

Published: Dec. 10, 2024

Viruses represent a diverse pool of obligate parasites that infect virtually every known organism, as such, their study is incredibly valuable for range fields including public health, medicine, agriculture, and ecology, the development biomedical technologies. Having evolved over millions years, each virus has unique often complicated biology, must be characterized on case-by-case basis, even between strains same taxon. Owing to its nanoscale spatial resolution, atomic force microscopy (AFM) represents powerful tool exploring structural features, kinetics binding host cell ligands, virion self-assembly, budding behaviors. Through availability numerous chemistries advances in imaging modes, AFM able explore complex web host-virus interactions life-cycle at single level, features level individual bonds molecules. Due wide array techniques developed data analysis approaches available, can provide information cannot furnished by other modalities, especially level. Here, we highlight methods obtained through use AFM, demonstrating both utility versatility viruses. As technology continues rapidly evolve, likely remain an integral part research, providing important insight into many aspects virology.

Language: Английский

Citations

1