OmpA controls order in the outer membrane and shares the mechanical load DOI Creative Commons
Georgina Benn,

Cristiana Borrelli,

Dheeraj Prakaash

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(50)

Published: Dec. 4, 2024

OmpA, a predominant outer membrane (OM) protein in Escherichia coli , affects virulence, adhesion, and bacterial OM integrity. However, despite more than 50 y of research, the molecular basis for role OmpA has remained elusive. In this study, we demonstrate that organizes lattice mechanically connects it to cell wall (CW). Using gene fusions, atomic force microscopy, simulations, microfluidics, show β-barrel domain is critical maintaining permeability barrier, but both CW–binding domains are necessary enhance envelope’s strength. integrates compressive properties with tensile strength CW, forming robust composite increases overall This coupling likely underpins ability entire envelope function as cohesive, resilient structure, survival bacteria.

Language: Английский

Computational Methods for Modeling Lipid-Mediated Active Pharmaceutical Ingredient Delivery DOI Creative Commons
Markéta Paloncýová, Mariana Valério, Ricardo Nascimento dos Santos

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Lipid-mediated delivery of active pharmaceutical ingredients (API) opened new possibilities in advanced therapies. By encapsulating an API into a lipid nanocarrier (LNC), one can safely deliver APIs not soluble water, those with otherwise strong adverse effects, or very fragile ones such as nucleic acids. However, for the rational design LNCs, detailed understanding composition-structure-function relationships is missing. This review presents currently available computational methods LNC investigation, screening, and design. The state-of-the-art physics-based approaches are described, focus on molecular dynamics simulations all-atom coarse-grained resolution. Their strengths weaknesses discussed, highlighting aspects necessary obtaining reliable results simulations. Furthermore, machine learning, i.e., data-based approach to lipid-mediated introduced. data produced by experimental theoretical provide valuable insights. Processing these help optimize LNCs better performance. In final section this Review, computer reviewed, specifically addressing compatibility

Language: Английский

Citations

2
Systematic Approach to Parametrization of Disaccharides for the Martini 3 Coarse-Grained Force Field DOI Creative Commons
Astrid F. Brandner, Iain P. S. Smith, ‪Siewert J. Marrink

et al.

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Sugars are ubiquitous in biology; they occur all kingdoms of life. Despite their prevalence, have often been somewhat neglected studies structure-dynamics-function relationships macromolecules to which attached, with the exception nucleic acids. This is largely due inherent difficulties not only studying conformational dynamics sugars using experimental methods but indeed also resolving static structures. Molecular (MD) simulations offer a route prediction ensembles and time-dependent behavior glycosylated macromolecules. However, at all-atom level detail, MD too computationally demanding allow systematic investigation molecular interactions systems interest. To overcome this, large scale complex biological profited from advances coarse-grained (CG) simulations. Perhaps most widely used CG force field for biomolecular Martini. Here, we present parameter set glucose- mannose-based disaccharides Martini 3. The generation parameters atomistic trajectories automated as fully possible, where provide details protocol manual intervention.

Language: Английский

Citations

1
Improved Free-Energy Estimates for the Permeation of Bulky Antibiotic Molecules through Porin Channels Using Temperature-Accelerated Sliced Sampling DOI Creative Commons
Abhishek Acharya, Ulrich Kleinekathöfer

Journal of Chemical Theory and Computation, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

The estimation of accurate free energies for antibiotic permeation via the bacterial outer-membrane porins has proven to be challenging. Atomistic simulations process suffer from sampling issues that are typical systems with complex and slow dynamics, even application advanced methods. Ultimately, objective is obtain potential mean force (PMF) a large set antibiotics predict rates. Therefore, computational expense becomes an important criterion as well. Simulation studies on similar processes have shown both scheme employed procedure used generation initial states can critically affect quality estimates obtained respective overhead. temperature-accelerated sliced method (TASS) been partly address efficient degrees freedom by enabling simultaneous biasing number collective variables. In this work, we investigate effect input conformations convergence free-energy TASS simulations. particular, compare steered molecular dynamics (MD)-based in previous Monte Carlo pathway search method, which approximate trajectories minimum perturbation protein channel. We tested different setups enrofloxacin through OmpK35 OmpE35. best setup shows improved agreement between independent PMFs cases at much lower cost.

Language: Английский

Citations

0
Polymyxin B1 in the E. coli inner membrane: a complex story of protein and lipopolysaccharide mediated insertion DOI Creative Commons

Dhanushka Weerakoon,

Jan K. Marzinek, Conrado Pedebos

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 107754 - 107754

Published: Sept. 1, 2024

Language: Английский

Citations

1
OmpA controls order in the outer membrane and shares the mechanical load DOI Creative Commons
Georgina Benn,

Cristiana Borrelli,

Dheeraj Prakaash

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(50)

Published: Dec. 4, 2024

OmpA, a predominant outer membrane (OM) protein in Escherichia coli , affects virulence, adhesion, and bacterial OM integrity. However, despite more than 50 y of research, the molecular basis for role OmpA has remained elusive. In this study, we demonstrate that organizes lattice mechanically connects it to cell wall (CW). Using gene fusions, atomic force microscopy, simulations, microfluidics, show β-barrel domain is critical maintaining permeability barrier, but both CW–binding domains are necessary enhance envelope’s strength. integrates compressive properties with tensile strength CW, forming robust composite increases overall This coupling likely underpins ability entire envelope function as cohesive, resilient structure, survival bacteria.

Language: Английский

Citations

1