Biophysics

Emergence of specific binding and catalysis from a designed generalist binding protein

1. Yuda Chen
2. Sagar Bhattacharya
3. Lena Bergmann
4. Galen J. Correy
5. Sophia K. Tan
6. Kaipeng Hou
7. Justin Biel
8. Lei Lu
9. Ian Bakanas
10. Alexander N. Volkov
11. Ivan V. Korendovych
12. Nicholas F. Polizzi
13. James S. Fraser
14. William F. DeGrado

Reviewed by Arcadia Science

Expanding automated multiconformer ligand modeling to macrocycles and fragments

1. Jessica Flowers
2. Nathaniel Echols
3. Galen J Correy
4. Priyadarshini Jaishankar
5. Takaya Togo
6. Adam R Renslo
7. Henry van den Bedem
8. James S Fraser
9. Stephanie A Wankowicz

• Curated by eLife

  eLife Assessment

  The work presents a valuable extension of qFit-ligand, a computational method for modeling conformational heterogeneity of ligands in X-ray crystallography and cryo-EM density maps. The authors provide solid evidence of improved capabilities through careful validation against the previous version, particularly in expanding ligand sampling within conformational space. Such improvements suggest practical utility for challenging applications, including macrocyclic compound modeling and crystallographic drug fragment screening.

Reviewed by Arcadia Science, eLife

Impacts of structural properties of myosin II filaments on force generation

1. Shihang Ding
2. Pei-En Chou
3. Shinji Deguchi
4. Taeyoon Kim

• Curated by eLife

  eLife Assessment

  The authors present a useful agent-based model to study the tensile force generated by myosin mini-filaments in actin systems (bundles and networks); by numerically solving a mechanical model of myosin-II filaments, the authors provide insights into how the geometry of the molecular components and their elastic responses determine the force production. This work is of interest to biophysicists (in particular theoreticians) investigating force generation of motor molecules from a biomechanical engineering and physics perspective. The authors convincingly show that cooperative effects between multiple myosin filaments can enhance the total force generated, but not the efficiency of force generation (force per myosin) if passive cross-linkers are present. This work would benefit from a more extensive discussion of the physiological relevance of the results in view of the existing experimental literature, and how the principles that govern the behavior could be different for different motor proteins.

Reviewed by eLife

Quantifying Intracellular Mechanosensitive Response upon Spatially Defined Mechano-Chemical Triggering

1. Elaheh Zare-Eelanjegh
2. Renard TM Lewis
3. Ines Lüchtefeld
4. Ulrike Kutay
5. Tomaso Zambelli

• Curated by eLife

  eLife Assessment

  This valuable study provides evidence that the integration of the nuclear envelope into the endoplasmic reticulum provides a mechanism for mechanical integration across this continuous membrane system. If robustly demonstrated, this work would open up new avenues for studying organelle membrane tension homeostasis. While the evidence is largely convincing and carefully quantified, a key limitation is the absence of data demonstrating that microinjection of cytoskeleton-depolymerizing drugs locally disrupts the target network.

Reviewed by eLife

AlphaFold as a Prior: Experimental Structure Determination Conditioned on a Pretrained Neural Network

1. Alisia Fadini
2. Minhuan Li
3. Airlie J. McCoy
4. Thomas C. Terwilliger
5. Randy J. Read
6. Doeke Hekstra
7. Mohammed AlQuraishi

Reviewed by PREreview

Atomistic simulation of voltage activation of a truncated BK channel

1. Zhiguang Jia
2. Jianhan Chen

• Curated by eLife

  eLife Assessment

  This valuable study addresses the structural basis of voltage-activation of BK channels using atomistic simulations of several microseconds, to assess conformational changes that underlie both voltage-sensing and gating of the pore. The findings, including movement of specific charged residues, combined with the degree to which these movements are coupled to pore movements, provide a solid basis for understanding voltage-gating mechanisms in this class of channels. This paper will likely be of interest to ion channel biologists and biophysicists focused on voltage-dependent channel gating mechanisms.

Reviewed by eLife

Noninvasive ultrasound targeted modulation of calcium influx in splenic immunocytes potentiates antineoplastic immunity attenuating hepatocellular carcinoma proliferation

1. Wei Dong
2. Guihu Wang
3. Senyang Li
4. Yichao Chai
5. Qian Wang
6. Yucheng Li
7. Qiaoman Fei
8. Yujin Zong
9. Jing Geng
10. Pengfei Liu
11. Zongfang Li

• Curated by eLife

  eLife Assessment

  This valuable study presents an innovative noninvasive immunotherapeutic strategy for hepatocellular carcinoma by combining ultrasound stimulation with calcium-loaded nanodroplets to activate splenic immune responses. The authors provide solid preclinical data, including single-cell transcriptomic analyses and evidence of tumor growth suppression, supported by a creative and well-executed methodology. Further validation of the calcium signaling mechanisms and assessment of long-term safety will strengthen the translational potential of this approach. The work will be of broad interest to researchers in oncology, immunotherapy, and biomedical engineering.

Reviewed by eLife

High-resolution cryo-EM structures of small protein–ligand complexes near the theoretical size limit

1. Kunwoong Park
2. Youngki Yoo
3. Hyunbum Jeon
4. Kiju Choi
5. Eunju Kwon
6. Hyun-Ho Lim
7. Dong Young Kim
8. Kyoung Tai No

Reviewed by PREreview

Distinct energetic blueprints diversify function of conserved protein folds

1. Malcolm L. Wells
2. Chenlin Lu
3. Daniel Sultanov
4. Kyle C. Weber
5. Erin Ahern
6. Zhen Gong
7. Ethan Chen
8. Anum Glasgow

Reviewed by PREreview

Toward stable replication of genomic information in pools of RNA molecules

1. Ludwig Burger
2. Ulrich Gerland

• Curated by eLife

  eLife Assessment

  This important theoretical study examines the possibility of encoding genomic information in a collective of short overlapping strands (e.g., the Virtual Circular Genome (VCG) model). The study presents convincing theoretical arguments, simulations and comparisons to experimental data to point at potential features and limitations of such distributed collective encoding of information. The work should be of relevance to colleagues interested in molecular information processing and to those interested in pre-Central Dogma or prebiotic models of self-replication.

Reviewed by eLife