Biophysics

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

Ab initio prediction of specific phospholipid complexes and membrane association of HIV-1 MPER antibodies by multi-scale simulations

1. Colleen A Maillie
2. Kiana Golden
3. Ian A Wilson
4. Andrew B Ward
5. Marco Mravic

• Curated by eLife

  eLife Assessment

  This valuable study reports multi-scale molecular dynamics simulations to investigate a class of highly potent antibodies that simultaneously engage with the HIV-1 Envelope trimer and the viral membrane. The work provides insights into how broadly neutralizing antibodies associate with lipids proximal to membrane-associated epitopes to drive neutralization. After extensive revision, the level of evidence is considered solid, although a quantitative assessment of the underlying energetics remain difficult to obtain.

Reviewed by eLife

Molecular dynamics simulations illuminate the role of sequence context in the ELF3-PrD-based temperature sensing mechanism in plants

1. Richard J Lindsay
2. Rafael Giordano Viegas
3. Vitor BP Leite
4. Philip A Wigge
5. Sonya M Hanson

• Curated by eLife

  eLife Assessment

  In this potentially valuable computational study, the authors conducted atomistic and coarse-grained simulations to probe the temperature-dependent phase behaviors of ELF3, a disordered component of the evening complex in plant. The results aim to highlight the role of polyQ tracts in modulating the temperature sensitivity. The level of evidence is considered incomplete, due to the lack of systematic calibration of the coarse-grained model and limited statistical uncertainty analysis, especially considering the relatively subtle nature of the differences due to temperature change.

Reviewed by eLife

Motor clustering enhances kinesin-driven vesicle transport

1. Rui Jiang
2. Qingzhou Feng
3. Daguan Nong
4. You Jung Kang
5. David Sept
6. William O. Hancock

Reviewed by preLights

Reversing protonation of weakly basic drugs greatly enhances intracellular diffusion and decreases lysosomal sequestration

1. Debabrata Dey
2. Shir Marciano
3. Anna Poryval
4. Ondřej Groborz
5. Lucie Wohlrabova
6. Tomás Slanina
7. Gideon Schreiber

• Curated by eLife

  eLife Assessment

  This is a valuable study on the diffusion rates of drug molecules in human-derived cells, presenting convincing data indicating that their diffusion behavior depends on their charged state. It proposes that blocking drug protonation enhances diffusion and fractional recovery, suggesting improved intracellular availability of weakly basic drugs. The findings are significant for drug design and understanding the biophysical behavior of small molecules in cells.

Reviewed by eLife

Conformational dynamics of a nicotinic receptor neurotransmitter site

1. Mrityunjay Singh
2. Dinesh C Indurthi
3. Lovika Mittal
4. Anthony Auerbach
5. Shailendra Asthana

• Curated by eLife

  eLife Assessment

  This useful work provides insight into agonist binding to nicotinic acetylcholine receptors, which is the stimulus for channel activation that regulates muscle contraction at the neuromuscular junction. The authors use in silico methods to explore the transient conformational change from a low to high affinity agonist-bound conformation as occurs during channel opening, but for which structural information is lacking owing to its transient nature. The simulations indicating that ligands flip ~180 degrees in the binding site as it transitions from a low to high affinity bound conformation are solid. A limitation is the approximation of binding energies using Poisson-Boltzmann Surface Area and mismatch between calculated and experimental binding energies for two of the four ligands tested. Nonetheless, this work presents an intriguing picture for the nature of a transient conformational change at the agonist binding site correlated with channel opening.

Reviewed by eLife

Targeted anticancer pre-vinylsulfone covalent inhibitors of carbonic anhydrase IX

1. Aivaras Vaškevičius
2. Denis Baronas
3. Janis Leitans
4. Agnė Kvietkauskaitė
5. Audronė Rukšėnaitė
6. Elena Manakova
7. Zigmantas Toleikis
8. Algirdas Kaupinis
9. Andris Kazaks
10. Marius Gedgaudas
11. Aurelija Mickevičiūtė
12. Vaida Juozapaitienė
13. Helgi B Schiöth
14. Kristaps Jaudzems
15. Mindaugas Valius
16. Kaspars Tars
17. Saulius Gražulis
18. Franz-Josef Meyer-Almes
19. Jurgita Matulienė
20. Asta Zubrienė
21. Virginija Dudutienė
22. Daumantas Matulis

• Curated by eLife

  eLife Assessment

  This paper reports the synthesis of covalent inhibitors bearing a unique fragment as a protected covalent warhead for irreversible binding to histidine in carbonic anhydrase (CA) enzymes. These findings are important due to the broad utility of the approach for covalent drug discovery applications and could have long-term impacts on related covalent targeting approaches. The data convincingly support the main conclusions of the paper.

Reviewed by eLife

CTFFIND5 provides improved insight into quality, tilt, and thickness of TEM samples

1. Johannes Elferich
2. Lingli Kong
3. Ximena Zottig
4. Nikolaus Grigorieff

• Curated by eLife

  eLife Assessment

  This valuable work presents the latest version of CTFFIND, which is the most popular software for determination of the contrast transfer function (CTF) in cryo-electron microscopy. CTFFIND5 estimates and considers acquisition geometry and sample thickness, which leads to improved CTF determination. The paper describes compelling evidence that CTFFIND5 finds better CTF parameters than previous methods, in particular for tilted samples (e.g. for cryo-electron tomography) or where thickness is an issue (e.g. cellular samples, or electron microscopy at low voltages).

Reviewed by eLife

Ligand-coupled conformational changes in a cyclic nucleotide-gated ion channel revealed by time-resolved transition metal ion FRET

1. Pierce Eggan
2. Sharona E Gordon
3. William N Zagotta

• Curated by eLife

  eLife Assessment

  This valuable study uses fluorescence lifetime imaging and steady-state and time-resolved transition metal ion FRET to characterize conformational transitions in the isolated cyclic nucleotide binding domain of a bacterial CNG channel. The data are compelling and support the authors' conclusions. The results advance the understanding of allosteric mechanisms in CNBD channels and have theoretical and practical implications for other studies of protein allostery. A limitation is that only the cytosolic fragments of the channel were studied.

Reviewed by eLife