Should Artificial Intelligence Play a Durable Role in Biomedical Research and Practice? DOI Open Access
Pierre Bongrand

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(24), С. 13371 - 13371

Опубликована: Дек. 13, 2024

During the last decade, artificial intelligence (AI) was applied to nearly all domains of human activity, including scientific research. It is thus warranted ask whether AI thinking should be durably involved in biomedical This problem addressed by examining three complementary questions (i) What are major barriers currently met investigators? suggested that during 2 decades there a shift towards growing need elucidate complex systems, and this not sufficiently fulfilled previously successful methods such as theoretical modeling or computer simulation (ii) potential meet aforementioned need? it recent well-suited perform classification prediction tasks on multivariate possibly help data interpretation, provided their efficiency properly validated. (iii) Recent representative results obtained with machine learning suggest may comparable displayed operators. concluded play an important role practice. Also, already other physics, combining conventional might generate further progress new applications, involving heuristic interpretation.

Язык: Английский

Theory and Examples of Catch Bonds DOI Creative Commons
Wolfgang Quapp, Josep María Bofill

The Journal of Physical Chemistry B, Год журнала: 2024, Номер 128(17), С. 4097 - 4110

Опубликована: Апрель 18, 2024

We discuss slip bonds, catch and the tug-of-war mechanism using mathematical arguments. The aim is to explain theoretical tool of molecular potential energy surfaces (PESs). For this, we propose simple 2-dimensional surface models demonstrate how a molecule under an external force behaves. Examples are selectins. Catch in particular, explained more detail, they contrasted bonds. can support special two-dimensional PESs for E- L-selectin which allow bond property. that Newton trajectories (NT) powerful tools describe these phenomena. NTs form background mechanochemistry.

Язык: Английский

Процитировано

5
To a mechanical model of synthetic catch-bonds DOI Creative Commons
Wolfgang Quapp, Josep María Bofill, Kerim C. Dansuk

и другие.

Journal of Mathematical Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Май 8, 2025

Язык: Английский

Процитировано

0
A direct computational assessment of vinculin–actin unbinding kinetics reveals catch-bonding behavior DOI Creative Commons
Willmor J. Peña Ccoa, Fatemah Mukadum, Aubin Ramon

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(21)

Опубликована: Май 21, 2025

Vinculin forms a catch bond with the cytoskeletal polymer actin, displaying an increased lifetime upon force application. Notably, this behavior depends on direction of applied force, which has significant implications for cellular mechanotransduction. In work, we present comprehensive molecular dynamics simulation study, employing enhanced sampling techniques to investigate thermodynamic, kinetic, and mechanistic aspects phenomenon at physiologically relevant forces. We dissect mechanism in shifts vinculin between either weakly or strongly bound state. Our results demonstrate that models these states have unbinding times consistent those from single-molecule studies, suggest both some intrinsic catch-bonding behavior. provide atomistic insight into behavior, show how directional pulling can promote strong weak Crucially, our strategy be extended measure difficult-to-capture effects small mechanical forces biomolecular systems general, involved mechanotransduction more specifically.

Язык: Английский

Процитировано

0
Engineering tunable catch bonds with DNA DOI Creative Commons
Micah Yang, David Bakker, Isaac T. S. Li

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 12, 2024

Unlike most adhesive bonds, biological catch bonds strengthen with increased tension. This characteristic is essential to specific receptor-ligand interactions, underpinning adhesion dynamics, cell communication, and mechanosensing. While artificial have been conceived, the tunability of their behaviour limited. Here, we present fish-hook, a rationally designed DNA bond that can be finely adjusted wide range behaviours. We develop models design these structures experimentally validate different behaviours by single-molecule force spectroscopy. The fish-hook architecture supports vast sequence-dependent space, making it valuable tool for reprogramming interactions engineering force-strengthening materials. Biological counter-intuitively when pulled. authors tuneable made from study biomimetic creation

Язык: Английский

Процитировано

3
Force-dependent Reorganization and Mechanostability of the Izumo1:Juno Complex Involved in Human Fertilization DOI Creative Commons

Sean Boult,

Paulina Pacak, Byeongseon Yang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 18, 2024

Abstract Izumo1:Juno-mediated adhesion between sperm and egg cells is essential for mammalian sexual reproduction. However, conventional biophysical structural approaches have provided only limited functional insights. Using atomic force microscopy-based single- molecule spectroscopy all-atom steered molecular dynamic simulations, we explored the role of mechanical forces in regulating human Izumo1:Juno complex. Our findings reveal a multi-state catch bond capable withstanding up to 600 pN- mechanostability rarely observed among eukaryotic protein complexes. We further found that this was impaired infertility-associated mutant, JunoH177Q. Detailed dynamics simulations show how force-dependent reorganization complex engages new binding conformations achieve state high mechanostability. Overall, study significantly enhances our understanding underpinnings regulate fertilization.

Язык: Английский

Процитировано

0
Comment to: "Topology of molecular deformations induces triphasic catch bonding in selectin-ligand bonds" DOI Creative Commons
Wolfgang Quapp, Josep María Bofill

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 23, 2024

We contradict diverse mathematical claims of a paper by Casey O. Barkan and Robijn F. Bruinsma in PNAS 2024, 121, No. 6, e2315866121, former BioRxiv preprint from Sept.12,2023. It deals with the physical mechanisms protein-ligand catch bonding for family selectin proteins. Selectins exhibit slip, catch–slip, slip–catch–slip bonding.

Язык: Английский

Процитировано

0
Comment to: “Topology of molecular deformations induces triphasic catch bonding in selectin–ligand bonds” DOI
Wolfgang Quapp, Josep María Bofill

Опубликована: Сен. 30, 2024

We contradict diverse mathematical claims of a paper by Casey O. Barkan and Robijn F. Bruinsma in PNAS 2024, 121, No. 6, e2315866121, former BioRxiv preprint from Sept.12,2023. It deals with the physical mechanisms protein-ligand catch bonding for family selectin proteins. Selectins exhibit slip, catch–slip, slip–catch–slip bonding.

Язык: Английский

Процитировано

0
Comment on ”Exploring potential energy surfaces to reach saddle points above convex regions” [J. Chem. Phys. 160, 232501 (2024)] by M.Gunde et al. DOI Creative Commons
Wolfgang Quapp, Josep María Bofill

Опубликована: Дек. 12, 2024

We comment on the work convex regions of potential energy surface (PES) a molecule by M. Gunde; A. Jay; Poberžnik; N. Salles; Richard; G. Landa; Mousseau; L. Martin-Samos and Hemeryck[1]. In contrast to activation-relaxation technique nouveau (ARTn), in present we apply theory Newton trajectories (NTs) 2D PES. NTs have no problem traversing or concave The ARTn is compared with NTs.

Язык: Английский

Процитировано

0
Should Artificial Intelligence Play a Durable Role in Biomedical Research and Practice? DOI Open Access
Pierre Bongrand

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(24), С. 13371 - 13371

Опубликована: Дек. 13, 2024

During the last decade, artificial intelligence (AI) was applied to nearly all domains of human activity, including scientific research. It is thus warranted ask whether AI thinking should be durably involved in biomedical This problem addressed by examining three complementary questions (i) What are major barriers currently met investigators? suggested that during 2 decades there a shift towards growing need elucidate complex systems, and this not sufficiently fulfilled previously successful methods such as theoretical modeling or computer simulation (ii) potential meet aforementioned need? it recent well-suited perform classification prediction tasks on multivariate possibly help data interpretation, provided their efficiency properly validated. (iii) Recent representative results obtained with machine learning suggest may comparable displayed operators. concluded play an important role practice. Also, already other physics, combining conventional might generate further progress new applications, involving heuristic interpretation.

Язык: Английский

Процитировано

0