Biophysics

Surprising features of nuclear receptor interaction networks revealed by live-cell single-molecule imaging

1. Liza Dahal
2. Thomas GW Graham
3. Gina M Dailey
4. Alec Heckert
5. Robert Tjian
6. Xavier Darzacq

• Curated by eLife

  eLife Assessment

  This important study provides data that challenges the standard model that binding of Type 2 Nuclear Receptors to chromatin is limited by the available pool of their common heterodimerization partner Retinoid X Receptor. The evidence supporting the conclusions is compelling, utilizing state-of-the-art single-molecule microscopy. This work will be of broad interest to cell biologists who wish to determine limiting factors in gene regulatory networks.

Reviewed by eLife

Heterogeneity in ligand-bound TRPV1: A comparison of methods in cryo-EM and molecular dynamics simulation

1. Miro A. Astore
2. Robert Blackwell
3. David Silva-Sánchez
4. Pilar Cossio
5. Sonya M. Hanson

Reviewed by PREreview

Wavenumber-dependent transmission of subthreshold waves on electrical synapses network model of Caenorhabditis elegans

1. Iksoo Chang
2. Taegon Chung
3. Sangyeol Kim

• Curated by eLife

  eLife Assessment

  This study presents numerical results on a framework for understanding the dynamics of subthreshold waves in a network of electrical synapses modeled on the connectome data of the C elegans nematode. The strength of the evidence presented in favor of interference effects being a major component in subthreshold wave dynamics is inadequate and the approach is flawed. Substantial methodological issues are present, including altering the original network structure of the connectome without a clear justification and providing little motivation for the choice of numerical parameters values that were used.

Reviewed by eLife

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

1. Jingze Duan
2. Chen Song

• Curated by eLife

  eLife Assessment

  This valuable 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 finding that the ankyrin spring transmits force through torsional rather than compression forces may help understand the entire TRP channel family. The evidence is, however, considered to be still incomplete. It could be strengthened by testing how the channel responds to different twisting and compressional force magnitudes over longer simulation times to see a full gating motion, or to prove that the partial or initial motion observed relates to physiological gating. Experimental validation of reduced mechano-sensitivity through mutagenesis of proposed ankyrin/TRP domain coupling interactions would be best to enhance the manuscript.

Reviewed by eLife

Discovery of a heparan sulfate binding domain in monkeypox virus H3 as an anti-poxviral drug target combining AI and MD simulations

1. Bin Zheng
2. Meimei Duan
3. Yifen Huang
4. Shangchen Wang
5. Jun Qiu
6. Zhuojian Lu
7. Lichao Liu
8. Guojin Tang
9. Lin Cheng
10. Peng Zheng

• Curated by eLife

  eLife Assessment

  This work presents important findings regarding the interaction of the monkeypox virus (MPXV) attachment H3 protein with the cellular receptor heparan sulfate and the use of this information to develop antivirals potentially effective against all orthopoxviruses. Using a combination of state-of-the art computational and wet experiments the authors present convincing evidence to sustain their claims. These results will interest those working on basic orthopoxviruses biology and antiviral development.

Reviewed by eLife

Atomic-Level Free Energy Landscape Reveals Cooperative Symport Mechanism of Melibiose Transporter

1. Ruibin Liang
2. Lan Guan

• Curated by eLife

  eLife Assessment

  In this potentially important study, the authors employed advanced computational techniques to explore a detailed atomistic description of the mechanism and energetics of substrate translocation in the MelB transporter. The overall approach is solid and reveals the coupling between sodium binding and melibiose transport through a series of conformational transitions, and the results for a mutant are also in qualitative agreement with the experiment, providing further support to the computational analyses. Nevertheless, the level of evidence is considered incomplete since there are concerns regarding the convergence and initial guess of the string calculations, leaving doubts that the computed pathway does not reflect the most energetically favorable mechanism.

Reviewed by eLife

A direct computational assessment of vinculin-actin unbinding kinetics reveals catch bonding behavior

1. Willmor J Peña Ccoa
2. Fatemah Mukadum
3. Aubin Ramon
4. Guillaume Stirnemann
5. Glen M Hocky

Reviewed by PREreview

Interplay of condensate material properties and chromatin heterogeneity governs nuclear condensate ripening

1. Deb Sankar Banerjee
2. Tafadzwa Chigumira
3. Rachel M Lackner
4. Josiah C Kratz
5. David M Chenoweth
6. Shiladitya Banerjee
7. Huaiying Zhang

• Curated by eLife

  eLife Assessment

  In this potentially valuable study, the authors employed in vivo experiments and theoretical modeling to study the growth dynamics of nuclear condensates. They observed that condensates can exhibit distinct growth modes, as dictated by the competition between condensate surface tension and local elasticity of chromatin. While the theoretical model appears to capture the experimental observations, the level of evidence supporting the proposed growth mechanism is incomplete due to, among other limitations, the multiple fitting parameters and poorly justified Neo-Hookean elasticity.

Reviewed by eLife

Determining accurate conformational ensembles of intrinsically disordered proteins at atomic resolution

1. Kaushik Borthakur
2. Thomas R. Sisk
3. Francesco P. Panei
4. Massimiliano Bonomi
5. Paul Robustelli

Reviewed by PREreview

Enhanced bacterial chemotaxis in confined microchannels: Optimal performance in lane widths matching circular swimming radius

1. Caijuan Yue
2. Chi Zhang
3. Rongjing Zhang
4. Junhua Yuan

• Curated by eLife

  eLife Assessment

  This valuable study examines the effects of side-wall confinement on the chemotaxis of swimming bacteria in a shallow microfluidic channel. The authors present solid experimental evidence, combined with geometric analysis and numerical simulations of simplified models, showing that chemotaxis is enhanced when the distance between the side walls is comparable to the intrinsic radius of circular swimming near open surfaces. This study should be of interest to scientists specializing in bacteria-surface interactions.

Reviewed by eLife