Biophysics

Intelligent Resolution: Integrating Cryo-EM with AI-driven Multi-resolution Simulations to Observe the SARS-CoV-2 Replication-Transcription Machinery in Action

1. Anda Trifan
2. Defne Gorgun
3. Zongyi Li
4. Alexander Brace
5. Maxim Zvyagin
6. Heng Ma
7. Austin Clyde
8. David Clark
9. Michael Salim
10. David J. Hardy
11. Tom Burnley
12. Lei Huang
13. John McCalpin
14. Murali Emani
15. Hyenseung Yoo
16. Junqi Yin
17. Aristeidis Tsaris
18. Vishal Subbiah
19. Tanveer Raza
20. Jessica Liu
21. Noah Trebesch
22. Geoffrey Wells
23. Venkatesh Mysore
24. Thomas Gibbs
25. James Phillips
26. S. Chakra Chennubhotla
27. Ian Foster
28. Rick Stevens
29. Anima Anandkumar
30. Venkatram Vishwanath
31. John E. Stone
32. Emad Tajkhorshid
33. Sarah A. Harris
34. Arvind Ramanathan

Reviewed by ScreenIT

Low-affinity integrin states have faster ligand-binding kinetics than the high-affinity state

1. Jing Li
2. Jiabin Yan
3. Timothy A Springer

• Curated by eLife

  Evaluation Summary:

  Li, Yan and Springer report ligand binding on- and off-rates for three different conformations of α4β1 as well as α5β1 integrin. This is the first report that provides these numbers, which are important to understand the 'mode of integrin activation'. The study is - from a technical stand point - flawlessly performed and the calculated data is in perfect agreement with the previously published data.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

A mechano-osmotic feedback couples cell volume to the rate of cell deformation

1. Larisa Venkova
2. Amit Singh Vishen
3. Sergio Lembo
4. Nishit Srivastava
5. Baptiste Duchamp
6. Artur Ruppel
7. Alice Williart
8. Stéphane Vassilopoulos
9. Alexandre Deslys
10. Juan Manuel Garcia Arcos
11. Alba Diz-Muñoz
12. Martial Balland
13. Jean-François Joanny
14. Damien Cuvelier
15. Pierre Sens
16. Matthieu Piel

• Curated by eLife

  Evaluation Summary:

  The paper by Venkova et al. is a comprehensive study of mammalian cell volume dynamics during the common cellular process of adhesion and spreading on a flat substrate, osmotic changes, and mechanical confinement. The paper reveals a complex interplay between cell water/ion regulation, cytoskeletal processes, and mechanical deformation of the cell. The topic is important in cell physiology and should be of considerable interest to cell biologists, mechanobiologists and biophysicists.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

The pathogen-encoded signaling receptor Tir exploits host-like intrinsic disorder to assist infection

1. Marta F. M. Vieira
2. Guillem Hernandez
3. Tiago Veloso
4. Hugo Monteiro
5. Miguel Arbesú
6. Andreas Zanzoni
7. Tiago N. Cordeiro

Reviewed by Review Commons

How Does Temperature Affect the Dynamics of SARS-CoV-2 M Proteins? Insights from Molecular Dynamics Simulations

1. Soumya Lipsa Rath
2. Madhusmita Tripathy
3. Nabanita Mandal

Reviewed by ScreenIT

Dynamic allostery highlights the evolutionary differences between the CoV-1 and CoV-2 main proteases

1. Paul Campitelli
2. Jin Lu
3. S. Banu Ozkan

Reviewed by ScreenIT

Nanofluidic chips for cryo-EM structure determination from picoliter sample volumes

1. Stefan T Huber
2. Edin Sarajlic
3. Roeland Huijink
4. Felix Weis
5. Wiel H Evers
6. Arjen J Jakobi

• Curated by eLife

  Evaluation Summary:

  Sample preparation for single-particle electron cryo-microscopy (cryo-EM) remains a bottleneck of this technique. The sample ice thickness cannot be accurately controlled, molecules may display strongly preferred orientations that make more elaborate data collection schemes necessary, and the sample may degrade at the air-water interface before it is finally frozen. In their pioneering work, the authors describe a prototype of a new microfluidic device that addresses some of these problems, including a refreshingly objective and critical discussion about the pros and cons of this novel approach. While some development will be required for this method to become mainstream, it has the potential to become a powerful alternative to the conventional workflow of single-particle cryo-EM, enabling full automation and making sample preparation highly reproducible.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Mechanistic Insights into the Effects of Key Mutations on SARS-CoV-2 RBD-ACE2 Binding

1. Abhishek Aggarwal
2. Supriyo Naskar
3. Nikhil Maroli
4. Biswajit Gorai
5. Narendra M. Dixit
6. Prabal K. Maiti

Reviewed by ScreenIT

An empirical energy landscape reveals mechanism of proteasome in polypeptide translocation

1. Rui Fang
2. Jason Hon
3. Mengying Zhou
4. Ying Lu

• Curated by eLife

  Evaluation Summary:

  AAA+ ATPases consume chemical energy in form of ATP to catalyze essential cellular reactions. Here, computational and biochemical approaches are used to model how the six subunits of the AAA+ ATPase Rpt1-6 coordinate their enzymatic activity with each other to exert unidirectional pulling forces on target polypeptide chains that promote protein unfolding. Although the technical aspects of the work are sometimes difficult to follow, the findings indicate that the order in which ATPase active sites fire is generally sequential, much like a rotary engine. The system can tolerate "misfires" - instances in which a subunit fails to hydrolyze ATP - by skipping the problematic subunit. The work should appeal to the broad AAA+ community and researchers trying to understand the biophysical principles by which complex biological machines operate.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Supramolecular Organization of SARS-CoV and SARS-CoV-2 Virions Revealed by Coarse-Grained Models of Intact Virus Envelopes

1. Beibei Wang
2. Changqing Zhong
3. D. Peter Tieleman

Reviewed by ScreenIT