Biophysics

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

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

• Curated by eLife

  eLife Assessment

  This 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

Protein phase change batteries drive innate immune signaling and cell fate

1. Alejandro Rodriguez Gama
2. Tayla Miller
3. Shriram Venkatesan
4. Jeffrey J. Lange
5. Jianzheng Wu
6. Xiaoqing Song
7. Dan Bradford
8. Malcolm Cook
9. Jay R. Unruh
10. Randal Halfmann

• Curated by eLife

  eLife Assessment

  This valuable study investigates the self-assembly activity of death-fold domains. The data collected using advanced microscopy and distributed amphifluoric FRET-based flow cytometry methods provide solid evidence for the conclusions, although the interpretations based on these conclusions remain speculative in some cases. This paper is broad interest to those studying a variety of biological pathways involved in inflammatory responses and various forms of cell death.

Reviewed by eLife

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

1. Majid Malboubi
2. Mohammad Hadi Esteki
3. Lulu IT Korsak
4. Ryan J Petrie
5. Emad Moeendarbary
6. 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

Allosteric effects of the coupling cation in melibiose transporter MelB

1. Parameswaran Hariharan
2. Yuqi Shi
3. Rosa Viner
4. Lan Guan

• Curated by eLife

  eLife Assessment

  This manuscript presents useful insights into the molecular basis underlying the positive cooperativity between the co-transported substrates (galactoside sugar and sodium ion) in the melibiose transporter MelB. Building on years of previous studies, this work improves on the resolution of previously published structures and reports the presence of a water molecule in the sugar binding site that would appear to be key for its recognition, introduces further structures bound to different substrates, and utilizes HDX-MS to further understand the positive cooperativity between sugar and the co-transported sodium cation. Although the experimental work is solid, the presentation of the data lacks clarity, and in particular, the HDX-MS data interpretation requires further explanation in both methodology and discussion, as well as a clearer description of the new insight that is obtained in relation to previous studies. The work will be of interest to biologists and biochemists working on cation-coupled symporters, which mediate the transport of a wide range of solutes across cell membranes.

Reviewed by eLife

In silico design and validation of high-affinity RNA aptamers for SARS-CoV-2 comparable to neutralizing antibodies

1. Yanqing Yang
2. Lulu Qiao
3. Yangwei Jiang
4. Zhiye Wang
5. Dong Zhang
6. Damiano Buratto
7. Liquan Huang
8. Ruhong Zhou

• Curated by eLife

  eLife Assessment

  This study presents a computational-experimental workflow for optimizing RNA aptamers targeting SARS-CoV-2 RBD. While the integrated approach combining docking, molecular dynamics, and experimental validation shows some promise, the useful findings are limited by the extremely weak binding affinities (>100 µM KD) and restriction to a single target system. The evidence is incomplete, with experimental design issues in the antibody competition assays and a lack of specificity testing undermining confidence in the conclusions.

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