Biophysics

Twist is the key to the gating of mechanosensitive ion channel NOMPC

1. Jingze Duan
2. Chen Song

• Curated by eLife

  eLife Assessment

  This study uses steered molecular dynamics simulations to interrogate force transmission in the mechanosensitive NOMPC channel, which plays roles including soft-touch perception, auditory function, and locomotion. The valuable finding that the ankyrin spring transmits force through torsional rather than compression forces may help understand the entire TRP channel family. The evidence is considered to be solid, although full opening of the channel is not seen, and it has been noted that experimental validation of reduced mechanosensitivity through mutagenesis of proposed ankyrin/TRP domain coupling interactions would help substantiate the findings.

Reviewed by eLife

Crossover in aromatic amino acid interaction strength between tyrosine and phenylalanine in biomolecular condensates

1. David De Sancho
2. Xabier Lopez

• Curated by eLife

  eLife Assessment

  This important study uses advanced computational methods to elucidate how environmental dielectric properties influence the interaction strengths of tyrosine and phenylalanine in biomolecular condensates. The evidence supporting the claims of the authors is convincing, as the simulations are performed rigorously providing mechanistic insights into the origin of the differences between the two aromatic amino acids considered. This study will be of broad interest to researchers studying biomolecular phase separation.

Reviewed by eLife

Protein language model identifies disordered, conserved motifs implicated in phase separation

1. Yumeng Zhang
2. Jared Zheng
3. Bin Zhang

• Curated by eLife

  eLife Assessment

  This valuable study presents an analysis of evolutionary conservation in intrinsically disordered regions, identified as key drivers of phase separation, leveraging a protein language model. The strength of evidence presented is convincing overall, though the theoretical grounding could benefit from further development.

Reviewed by eLife

DIRseq as a method for predicting drug-interacting residues of intrinsically disordered proteins from sequences

1. Matt MacAinsh
2. Sanbo Qin
3. Huan-Xiang Zhou

• Curated by eLife

  eLife Assessment

  This important study presents a sequence-based method for predicting drug-interacting residues in intrinsically disordered proteins (IDPs), addressing a significant challenge in understanding small-molecule:IDP interactions. The findings have solid support through examples underscoring the role of aromatic interactions. While predicted binding sites remain coarse, validation was done on a total of 10 IDPs at varying depths. The method builds on the authors' previous work and, with ad hoc modifications, is poised to benefit this emerging field.

Reviewed by eLife

Transport kinetics across interfaces between coexisting liquid phases

1. Lars Hubatsch
2. Stefano Bo
3. Tyler S Harmon
4. Anthony A Hyman
5. Christoph A Weber
6. Frank Jülicher

• Curated by eLife

  eLife Assessment

  This study offers a valuable theoretical framework for quantifying molecular transport across interfaces between coexisting liquid phases, emphasizing interfacial resistance as a central factor governing transport kinetics. The mathematical derivations are solid. To enhance the paper's relevance and broaden its appeal, it would be helpful to clarify how the key equations connect to existing literature and to elucidate the physical mechanisms underlying scenarios that give rise to substantial interfacial resistance.

Reviewed by eLife

Salmonids elicit an acute behavioral response to heterothermal environments

1. Robert Naudascher
2. Stefano Brizzolara
3. Jonasz Slomka
4. Robert M Boes
5. Markus Holzner
6. Luiz GM Silva
7. Roman Stocker

• Curated by eLife

  eLife Assessment

  This valuable paper investigates how fish avoid thermal disturbances that occur on fast timescales. The authors use a creative experimental approach that quickly creates a vertical thermal interface, which they combine with careful behavioral analyses. The evidence supporting their results is solid, but there is a potential confounding factor between temperature and vertical positioning, and characterization of the thermal interface would greatly assist in interpreting the results.

Reviewed by eLife

The cytoplasm of living cells can sustain transient and steady intracellular pressure gradients

1. Majid Malboubi
2. Mohammad Hadi Esteki
3. Malti B Vaghela
4. Lulu IT Korsak
5. Ryan J Petrie
6. Emad Moeendarbary
7. Guillaume Charras

• Curated by eLife

  eLife Assessment

  This important study combines imaginative and innovative experiments with a finite element modelling to demonstrate the relevance of poroelasticity in the mechanical properties of cells across physiologically relevant time and length scales. The authors present convincing evidence that cytosolic flows and pressure gradients can persist in cells with permeable membranes, generating spatially segregated influx and outflux zones. These findings are of interest to the cell biology and biophysics communities.

Reviewed by eLife

PARP1 inhibitors regulate PARP1 structure independent of DNA, reducing binding affinity for single strand breaks

1. Mark Pailing
2. Lotte van Beek
3. Taiana Maia de Oliveira
4. Maria M. Flocco
5. Bart W. Hoogenboom

Reviewed by Arcadia Science

Criticality-driven enhancer-promoter dynamics in Drosophila chromosomes

1. Gautham Ganesh
2. Jean-Bernard Fiche
3. Marcelo Nöllmann
4. Julien Mozziconacci

• Curated by eLife

  eLife Assessment

  This manuscript uses modeling approaches to provide mechanistic insight into the structural and dynamic properties of enhancer-promoter interactions in Drosophila. Given the interest in this field, this is a timely approach, and the results give useful insights by providing predictions about the processivity of cohesin loop extrusion in Drosophila and concluding that the compartmental interaction strength is poised near criticality in the coil-globule phase space. The evidence provided to support some of the conclusions is, however, incomplete and would be strengthened by better considering some of the caveats in the data used to constrain the models, such as the use of "homie" genetic elements in the dynamic data. There is insufficient evidence provided for the dynamics being criticality-driven, and in addition, consideration of alternative models would further strengthen the conclusions of the manuscript.

Reviewed by eLife

AF2χ: Predicting protein side-chain rotamer distributions with AlphaFold2

1. Matteo Cagiada
2. F. Emil Thomasen
3. Sergey Ovchinnikov
4. Charlotte M. Deane
5. Kresten Lindorff-Larsen

Reviewed by PREreview