Biophysics

Oligomerization enables the selective targeting of intrinsically disordered regions by small molecules

1. Stasė Bielskutė
2. Borja Mateos
3. Muhammad Awawdy
4. Carla Garcia-Cabau
5. Henri Niskanen
6. Carolina Sánchez-Zarzalejo
7. Lorenzo Bracaglia
8. Roberta Pierattelli
9. Isabella C. Felli
10. Marta Frigolé-Vivas
11. Jesús García
12. Antoni Riera
13. Denes Hnisz
14. Xavier Salvatella

Reviewed by PREreview

Opening and closing of a cryptic pocket in VP35 toggles it between two different RNA-binding modes

1. Upasana L Mallimadugula
2. Matthew A Cruz
3. Neha Vithani
4. Maxwell I Zimmerman
5. Gregory R Bowman

• Curated by eLife

  eLife Assessment

  This study provides important insights into how cryptic pockets play a role in shaping binding preferences of protein-nucleic acid interactions. By combining biochemical assays and state-of-the-art molecular dynamics simulations, mechanism underlying viral protein 35 (VP35) homologs to bind the backbone of double stranded RNA is presented. The evidence is compelling for molecular determinants that suggest two different dsRNA binding modes for VP35 and also underscores the evolutionary importance of these pockets.

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. While the data on comparison of scrambling competence is compelling, the evidence for outside-the-groove scramblase activity without experimental validation is missing and is based on a limited set of observed events.

Reviewed by eLife

Swirling motion of breast cancer cells radially aligns collagen fibers to enable collective invasion

1. Aashrith Saraswathibhatla
2. Md Foysal Rabbi
3. Sushama Varma
4. Vasudha Srivastava
5. Olga Ilina
6. Naomi Hassan Kahtan Alyafei
7. Louis Hodgson
8. Zev Gartner
9. Peter Friedl
10. Robert West
11. Taeyoon Kim
12. Ovijit Chaudhuri

Reviewed by preLights

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. While the method is convincing, it requires some adaptation for application to different proteins. The IDEA method is available and can be potentially used for predicting genome-wide protein-DNA binding sites.

Reviewed by eLife

Physical constraints and biological regulations underlie universal osmoresponses

1. Yiyang Ye
2. Qirun Wang
3. Jie Lin

• Curated by eLife

  eLife Assessment

  This manuscript develops a theoretical model of osmotic pressure adaptation in microbes by osmolyte production and wall synthesis. The prediction of a rapid increase in growth rate on osmotic shock is experimentally validated using fission yeast. By using phenomenological rules rather than detailed molecular mechanisms, the model can potentially apply to a wide range of microbes, providing important insights that would be of interest to the wider community studying the regulation of cell size and mechanics. The level of coarse-graining and the assumptions and limitations of the model have been well described, providing a convincing foundation for making predictions. However, further experimental work on the validity of the core assumptions across a range of microbial organisms is needed to assess the universality of the model.

Reviewed by eLife

Characterization of binding kinetics and intracellular signaling of new psychoactive substances targeting cannabinoid receptor using transition-based reweighting method

1. Soumajit Dutta
2. Diwakar Shukla

• Curated by eLife

  eLife Assessment

  A combination of molecular dynamics simulation and state-of-the-art statistical post-processing techniques provided valuable insight into GPCR-ligand dynamics. This manuscript provides solid evidence for differences in the binding/unbinding of classical cannabinoid drugs from new psychoactive substances. The results could aid in mitigating the public health threat these drugs pose.

Reviewed by eLife

Harnessing AlphaFold to reveal hERG channel conformational state secrets

1. Khoa Ngo
2. Pei-Chi Yang
3. Vladimir Yarov-Yarovoy
4. Colleen E Clancy
5. Igor Vorobyov

• Curated by eLife

  eLife Assessment

  This valuable study uses AlphaFold2 to guide the structural modelling of different states of the human voltage-gated potassium channel KV11.1, a key pharmacological drug target. Follow-up molecular dynamics and drug-docking simulations, combined with experimental characterization, offer convincing evidence supporting the models. The work shows potential for improving drug potency predictions in ion channel pharmacology.

Reviewed by eLife

Cellular coordination underpins rapid reversals in gliding filamentous cyanobacteria and its loss results in plectonemes

1. Jerko Rosko
2. Rebecca N Poon
3. Kelsey Cremin
4. Emanuele Locatelli
5. Mary Coates
6. Sarah JN Duxbury
7. Kieran Randall
8. Katie Croft
9. Chantal Valeriani
10. Marco Polin
11. Orkun S Soyer

• Curated by eLife

  eLife Assessment

  Using microscopy experiments and theoretical modelling, the authors present convincing evidence of cellular coordination in the gliding filamentous cyanobacterium Fluctiforma draycotensis. The results are fundamental for the understanding of cyanobacterial motility and the underlying molecular and mechanical pathways of cellular coordination.

Reviewed by eLife

Reconstitution of actomyosin networks in cell-sized liposomes reveals distinct mechanical roles of cytoskeletal organization in membrane shape remodeling

1. Makito Miyazaki
2. Fahmida Sultana Laboni
3. Taeyoon Kim

Reviewed by Arcadia Science