Biophysics

Activation mechanism of the human Smoothened receptor

1. Prateek D. Bansal
2. Soumajit Dutta
3. Diwakar Shukla

• Curated by Biophysics Colab

  Evaluation statement (22 August 2023)

  Bansal et al. present an atomistic view of the transition cascade of the class F GPCR Smoothened (Smo). The extensive long-range molecular dynamics simulations together with stochastic modelling provide theoretical insight into Smo activation and how this is modulated by different ligands. The work identifies testable hypotheses for functional studies of Smo and other class F GPCRs. Future simulations of regions beyond the seven-transmembrane bundle, particularly the cysteine-rich domain, will afford a more complete understanding of receptor activation.

  Biophysics Colab considers this to be a convincing computational study and recommends it to scientists interested in the conformational dynamics of class F GPCRs.

  (This evaluation by Biophysics Colab refers to version 2 of this preprint, which has been revised in response to peer review of version 1.)

Reviewed by Biophysics Colab

Absence of electron-transfer-associated changes in the time-dependent X-ray free-electron laser structures of the photosynthetic reaction center

1. Gai Nishikawa
2. Yu Sugo
3. Keisuke Saito
4. Hiroshi Ishikita

• Curated by eLife

  eLife assessment

  The manuscript describes valuable theoretical calculations focusing on the structural changes in the photosynthetic reaction center postulated by others based on time-resolved crystallography using X-ray free-electron laser (XFEL) (Dods et al., Nature, 2021). The authors provide solid arguments that calculated changes in redox potential Em and deformations using the XEFL structures may reflect experimental errors rather than real structural changes.

Reviewed by eLife

Allosteric inhibition of the T cell receptor by a designed membrane ligand

1. Yujie Ye
2. Shumpei Morita
3. Justin J Chang
4. Patrick M Buckley
5. Kiera B Wilhelm
6. Daniel DiMaio
7. Jay T Groves
8. Francisco N Barrera

• Curated by eLife

  eLife assessment

  The authors use a previously described technology of designing soluble transmembrane-targeting peptides, to interfere with the receptor function of the T cell receptor (TCR), which provides useful insights into the molecular mechanism of T cell activation. The designed PITCR peptide has functional effects, but the evidence for the proposed mechanism is still incomplete. With further data to support the conclusion, results from this study will be of interest to those studying the TCR as well as those seeking to use the TCR or its derivatives in synthetic biology studies and immunotherapy.

Reviewed by eLife

The Reissner fiber under tension in vivo shows dynamic interaction with ciliated cells contacting the cerebrospinal fluid

1. Celine Bellegarda
2. Guillaume Zavard
3. Lionel Moisan
4. Françoise Brochard-Wyart
5. Jean-François Joanny
6. Ryan S Gray
7. Yasmine Cantaut-Belarif
8. Claire Wyart

• Curated by eLife

  eLife assessment

  This exceptional work substantially advances our understanding of the mechanics of the Reissner's fibre (RF) by performing in-vivo experiments that track and analyze the behavior of the RF when it is cut and the behavior of ciliated cells touching the RF when contact is interrupted. The data is valuable and the conclusions are compelling. The work will be of broad interest to many research communities including developmental neuroscience and cilia biology.

Reviewed by eLife

CaMKII autophosphorylation can occur between holoenzymes without subunit exchange

1. Iva Lučić
2. Léonie Héluin
3. Pin-Lian Jiang
4. Alejandro G Castro Scalise
5. Cong Wang
6. Andreas Franz
7. Florian Heyd
8. Markus C Wahl
9. Fan Liu
10. Andrew JR Plested

• Curated by eLife

  eLife assessment

  This manuscript reports the fundamental finding that an oligomeric protein kinase, CaMKII, can be phosphorylated by another molecule of the holoenzyme in a manner that does not involve subunit exchange. The evidence for the main conclusion is compelling, supported by several independent experiments. If independently confirmed in future, the study will stand as having provided a novel regulatory mechanism for the autophosphorylation of this kinase. The work will be of broad interest to molecular and cellular neuroscientists as well as biochemists.

Reviewed by eLife

How accurately can one predict drug binding modes using AlphaFold models?

1. Masha Karelina
2. Joseph J Noh
3. Ron O Dror

• Curated by eLife

  eLife assessment

  This important study presents findings with broad implications for the use of AlphaFold2 models in ligand binding pose modeling, a common task in protein structure modeling. The computational experiments and analyses provide compelling results for the GPCR protein family data, but the conclusions are likely to apply also to other proteins and they will therefore be of interest to biophysicists, physical chemists, structural biologists, and anyone interested or involved in structure-based ligand discovery.

Reviewed by eLife

Emergence of flagella-like oscillations in single microtubules driven by collective dynein transport

1. Shivani A. Yadav
2. Neha Khetan
3. Dhruv Khatri
4. Chaitanya A. Athale

Reviewed by Review Commons

Biomimetic actin cortices shape cell-sized lipid vesicles

1. Lucia Baldauf
2. Felix Frey
3. Marcos Arribas Perez
4. Miroslav Mladenov
5. Michael Way
6. Timon Idema
7. Gijsje H. Koenderink

Reviewed by Arcadia Science

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