Biophysics

Dynamic allosteric networks drive adenosine A1 receptor activation and G-protein coupling

1. Miguel A Maria-Solano
2. Sun Choi

• Curated by eLife

  eLife assessment

  The authors describe the dynamics underlying allostery of the adenosine A1 receptor, providing valuable insights into the receptor's activation pathway. The enhanced sampling molecular dynamics simulations of available structural data, followed by network analysis, reveal transient conformational states and communication between functional regions. The authors carefully state the limitations of their work, including the restricted convergence of the free energy landscape and missing water-mediated hydrogen bond coordination. Collectively, they provide a convincing framework for advancing rational design strategies of specific modulators with desired modes of action.

  [Editors' note: this was originally reviewed and assessed by Biophysics Colab]

• Curated by Biophysics Colab

  Evaluation statement (16 June 2023)

  Maria-Solano and Choi present the dynamics underlying allostery of the adenosine A1 receptor, providing valuable insights into the receptor's activation pathway. The enhanced sampling molecular dynamics simulations of available structural data, followed by network analysis, reveal transient conformational states and communication between functional regions. The authors carefully state the limitations of their work, including the restricted convergence of the free energy landscape and missing water-mediated hydrogen bond coordination. Collectively, the findings provide a convincing framework to advance rational design strategies of specific modulators with desired modes of action.

  Biophysics Colab considers this to be a convincing study and recommends it to scientists interested in the structural dynamics, allosteric pathway activations, and free energy landscapes of GPCRs.

  (This evaluation by Biophysics Colab refers to version 5 of this preprint, which has been revised in response to peer review of versions 3 and 4.)

Reviewed by eLife, Biophysics Colab

Optimized path planning surpasses human efficiency in cryo-EM imaging

1. Yilai Li
2. Quanfu Fan
3. Ziping Xu
4. Emma Rose Lee
5. John Cohn
6. Veronique Demers
7. Ja Young Lee
8. Lucy Yip
9. Michael A. Cianfrocco
10. Seychelle M. Vos

• Curated by eLife

  eLife assessment

  Cryo-EM has become the dominant method in structural biochemistry, and making more efficient use of expensive microscope time is therefore of broad interest to academic and industrial users. The authors identify a bottleneck in cryoEM data collection, namely path optimization, and provide a valuable machine-learning model to overcome this bottleneck. The solid data presented suggests their model can replace a human operator to automate efficient data collection.

Reviewed by eLife

Conformational dynamics of lipid transfer domains provide a general framework to decode their functional mechanism

1. Sriraksha Srinivasan
2. Andrea Di Luca
3. Arun T. John Peter
4. Charlotte Gehin
5. Museer A. Lone
6. Thorsten Hornemann
7. Giovanni D’Angelo
8. Stefano Vanni

Reviewed by Review Commons

Free energy landscapes of KcsA inactivation

1. Sergio Pérez-Conesa
2. Lucie Delemotte

• Curated by eLife

  eLife assessment

  In this valuable study, advanced simulation methodologies are used to extract the mechanisms of inactivation for the potassium ion channel KcsA. The string method approach provides solid evidence that reveal features associated with the interplay between gate size and collapse of the selectivity filter, as well as remarkable differences between different force fields. While this manuscript does not address recent discoveries in K channel inactivation involving dilated selectivity filter structures obtained by Xray and cryo-EM, it does help us understand the KcsA constriction process. With added descriptions and analysis of collective variables, improved reproducibility of results, consistency between string method free energies and unbiased simulations, and improved transition rate calculation, this manuscript will be of interest to the ion channel field.

Reviewed by eLife

De novo identification of universal cell mechanics gene signatures

1. Marta Urbanska
2. Yan Ge
3. Maria Winzi
4. Shada Abuhattum
5. Syed Shafat Ali
6. Maik Herbig
7. Martin Kräter
8. Nicole Toepfner
9. Joanne Durgan
10. Oliver Florey
11. Martina Dori
12. Federico Calegari
13. Fidel-Nicolás Lolo
14. Miguel Á. del Pozo
15. Anna Taubenberger
16. Carlo V. Cannistraci
17. Jochen Guck

• Curated by eLife

  eLife assessment

  This important study uses machine learning-based network analysis on transcriptomic data from different tissue cell types to identify a small set of conserved (pan-tissue) genes associated with changes in cell mechanics. The new method is compelling and, together with rigorous in silico and experimental validation, provides convincing evidence for the claims. The study would be strengthened with an expanded set of validation (e.g. testing genes with hitherto unknown roles and different perturbation techniques), but will nonetheless be of broad interest to cell biologists, biophysicists, and bioengineers.

Reviewed by eLife

Dual nature of human ACE2 glycosylation in binding to SARS-CoV-2 spike

1. Ahmad Reza Mehdipour
2. Gerhard Hummer

Reviewed by ScreenIT

Structural Basis for Helicase-Polymerase Coupling in the SARS-CoV-2 Replication-Transcription Complex

1. James Chen
2. Brandon Malone
3. Eliza Llewellyn
4. Michael Grasso
5. Patrick M.M. Shelton
6. Paul Dominic B. Olinares
7. Kashyap Maruthi
8. Edward T. Eng
9. Hasan Vatandaslar
10. Brian T. Chait
11. Tarun M. Kapoor
12. Seth A. Darst
13. Elizabeth A. Campbell

Reviewed by ScreenIT

The Global and Local Distribution of RNA Structure throughout the SARS-CoV-2 Genome

1. Rafael de Cesaris Araujo Tavares
2. Gandhar Mahadeshwar
3. Han Wan
4. Nicholas C. Huston
5. Anna Marie Pyle

Reviewed by ScreenIT

Map of SARS-CoV-2 spike epitopes not shielded by glycans

1. Mateusz Sikora
2. Sören von Bülow
3. Florian E. C. Blanc
4. Michael Gecht
5. Roberto Covino
6. Gerhard Hummer

Reviewed by ScreenIT

Assessment of proton-coupled conformational dynamics of SARS and MERS coronavirus papain-like proteases: Implication for designing broad-spectrum antiviral inhibitors

1. Jack A. Henderson
2. Neha Verma
3. Robert C. Harris
4. Ruibin Liu
5. Jana Shen

Reviewed by ScreenIT