Biophysics

Structure and Cl- Conductance Properties of the Open State of Human CFTR

1. Zhi-Wei Zeng
2. Christopher E Ing
3. Régis Pomès

• Curated by eLife

  eLife Assessment

  This important study reports a detailed computational analysis of the CFTR ion channel's permeation mechanism, advancing our understanding of its structure-function relationship. The conclusions are based on extensive molecular dynamics simulations and thorough analysis, but the use of an approximate chloride ion model, known to underestimate key ion-protein interactions, leaves them incomplete without experimental or alternative computational validation. The work will be of interest to biophysicists working on CFTR and cystic fibrosis.

Reviewed by eLife

A thermodynamic framework for nonequilibrium self-assembly and force morphology tradeoffs in branched actin networks

1. Elisabeth Rennert
2. Suriyanarayanan Vaikuntanathan

• Curated by eLife

  eLife Assessment

  Rennert et al. developed a valuable thermodynamic framework to study the force response of branched actin networks from the crucial and unexplored perspective of energetic cost. They used the fact that the entropy production rate must be positive to derive inequalities that set limits on the maximum force produced by branched actin networks, and speculate that the dissipative cost beyond that required to move the load may be necessary to maintain an adaptive steady state. This work is highly innovative, but remains incomplete until the hypotheses of the model are better justified and the conclusions about the dissipative cost of the system are better established.

Reviewed by eLife

A conformational fingerprint for amyloidogenic light chains

1. Cristina Paissoni
2. Sarita Puri
3. Luca Broggini
4. Manoj K Sriramoju
5. Martina Maritan
6. Rosaria Russo
7. Valentina Speranzini
8. Federico Ballabio
9. Mario Nuvolone
10. Giampaolo Merlini
11. Giovanni Palladini
12. Shang-Te Danny Hsu
13. Stefano Ricagno
14. Carlo Camilloni

• Curated by eLife

  eLife Assessment

  This study addresses an important and longstanding question regarding the molecular mechanism of protein misfolding in Ig light chain (LC) amyloidosis (AL), a life-threatening condition. By combining advanced techniques, including small-angle X-ray scattering, molecular dynamics simulations, and hydrogen-deuterium exchange mass spectrometry, the authors provide convincing evidence that the "H state" distinguishes amyloidogenic from non-amyloidogenic LCs. These findings not only offer novel insights into LC structural dynamics but also hold promise for guiding therapeutic strategies in amyloidosis and will be of particular interest to structural biologists, biophysicists, and many others working on amyloid diseases.

Reviewed by eLife

Stability vs flexibility: reshaping archaeal membranes in silico

1. Miguel Amaral
2. Felix Frey
3. Xiuyun Jiang
4. Buzz Baum
5. Anđela Šarić

• Curated by eLife

  eLife Assessment

  This important study characterizes the mechanics and stability of bolalipids from archaeal membranes using molecular dynamics simulations. A mesoscale model of bolalipids is presented and evaluated across a series of membrane configurations. The evidence supporting the conclusions is convincing, demonstrating that mixtures of bolalipids and regular bilayer lipids in archaeal membranes enhance fluidity and stability.

Reviewed by eLife

ATP-release pannexin channels are gated by lysophospholipids

1. Erik Henze
2. Russell N. Burkhardt
3. Bennett W. Fox
4. Tyler J. Schwertfeger
5. Eric Gelsleichter
6. Kevin Michalski
7. Lydia Kramer
8. Margret Lenfest
9. Jordyn M. Boesch
10. Hening Lin
11. Frank C. Schroeder
12. Toshimitsu Kawate

• Curated by Biophysics Colab

  Evaluation Statement (5 February 2025)

  Pannexin (Panx) channels are a family of poorly understood large-pore channels that mediate the release of substrates like ATP from cells, yet the physiological stimuli that activate these channels remain poorly understood. The preprint by Henze et al. describes an elegant approach wherein activity-guided fractionation of mouse liver led to the discovery that lysophospholipids (LPCs) activate Panx1 and Panx2 channels expressed in cells or reconstituted into liposomes. The authors provide evidence that LPC-mediated activation of Panx1 is involved in joint pain and that Panx1 channels are required for the established effects of LPC on inflammasome activation in monocytes, suggesting that Panx channels play a role in inflammatory pathways. Overall, this important study reports a previously unanticipated mechanism wherein LPCs directly activate Panx channels.

  Biophysics Colab recommends this study to scientists investigating phospholipids, Panx channels, purinergic signalling and inflammation.

  Biophysics Colab has evaluated this study as one that meets the following criteria:

  • Rigorous methodology
  • Transparent reporting
  • Appropriate interpretation

  (This evaluation refers to version 3 of this preprint, which has been revised in response to peer review of versions 1 and 2.)

Reviewed by Biophysics Colab

Compound Mutations in the Abl1 Kinase Cause Inhibitor Resistance by Shifting DFG Flip Mechanisms and Relative State Populations

1. Gabriel Monteiro da Silva
2. Kyle Lam
3. David C Dalgarno
4. Brenda M Rubenstein

• Curated by eLife

  eLife Assessment

  This work uses enhanced sampling molecular dynamics methods to generate potentially useful information about a conformational change (the DFG flip) that plays a key role in regulating kinase function and inhibitor binding. The focus of the work is on the mechanism of conformational change and how mutations affect the transition. The evidence supporting the conclusions is incomplete.

Reviewed by eLife

Raman flow cytometry using time delay integration

1. Matthew Lindley
2. Toshiki Kubo
3. Stéphanie Devineau
4. Menglu Li
5. Jing Qiao
6. Takuya Yashiro
7. Shiroh Iwanaga
8. Kazuyo Moro
9. Katsumasa Fujita

Reviewed by Arcadia Science

Interpretable Protein-DNA Interactions Captured by Structure-Sequence Optimization

1. Yafan Zhang
2. Irene Silvernail
3. Zhuyang Lin
4. Xingcheng Lin

• Curated by eLife

  eLife Assessment

  This valuable work presents an interpretable protein-DNA Energy Associative (IDEA) model for predicting binding sites and affinities of DNA-binding proteins. The study provides a detailed description of the method, making it reproducible. However, the generalizability of the prediction model presents certain concerns, and the supporting evidence appears incomplete. Nonetheless, with a thorough re-examination of the training and testing procedures, this model can be widely applicable for predicting genome-wide protein-DNA binding sites.

Reviewed by eLife

Impacts of Structural Properties of Myosin II Filaments on Force Generation

1. Shihang Ding
2. Pei-En Chou
3. Shinji Deguchi
4. Taeyoon Kim

• Curated by eLife

  eLife Assessment

  The authors present a useful agent-based model to study the tensile force generated by myosin mini-filaments in actin systems (bundles and networks); by numerically solving a mechanical model of myosin-II filaments, the authors provide insights into how the geometry of the molecular components and their elastic responses determine the force production. This work is of interest to biophysicists (in particular theoreticians) investigating force generation of motor molecules from a biomechanical engineering and physics perspective. The authors convincingly show that cooperative effects between multiple myosin filaments can enhance the total force generated, but not the efficiency of force generation (force per myosin) if passive cross-linkers are present. This work would benefit from a more extensive discussion of the relevance of the results in view of the existing experimental literature.

Reviewed by eLife

Simulation-based survey of TMEM16 family reveals that robust lipid scrambling requires an open groove

1. Christina Alexandra Stephens
2. Niek van Hilten
3. Lisa Zheng
4. Michael Grabe

• Curated by eLife

  eLife Assessment

  This important study provides information on the TMEM16 family of membrane proteins, which play roles in lipid scrambling and ion transport. By simulating 27 structures representing five distinct family members, the authors captured hundreds of lipid scrambling events, offering insights into the mechanisms of lipid translocation and the specific protein regions involved in these processes. However, while the data on groove dilation is compelling, the evidence for outside-the-groove scramblase activity without experimental validation is inadequate and is based on a limited set of observed events.

Reviewed by eLife