npj Drug Discovery., Год журнала: 2025, Номер 2(1)
Опубликована: Июнь 4, 2025
Язык: Английский
The Journal of Physical Chemistry B, Год журнала: 2024, Номер 128(41), С. 9976 - 10042
Опубликована: Сен. 20, 2024
Since its inception nearly a half century ago, CHARMM has been playing central role in computational biochemistry and biophysics. Commensurate with the developments experimental research advances computer hardware, range of methods applicability have also grown. This review summarizes major that occurred after 2009 when last was published. They include following: new faster simulation engines, accessible user interfaces for convenient workflows, vast array analysis encompass quantum mechanical, atomistic, coarse-grained levels, as well extensive coverage force fields. In addition to providing current snapshot development, this may serve starting point exploring relevant theories tackling contemporary emerging problems biomolecular systems. is freely available academic nonprofit at https://academiccharmm.org/program.
Язык: Английский
Процитировано
28
Molecular Pharmaceutics, Год журнала: 2025, Номер unknown
Опубликована: Янв. 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
Язык: Английский
Процитировано
4
Nature Cell Biology, Год журнала: 2025, Номер unknown
Опубликована: Март 21, 2025
Abstract Prohibitins are a highly conserved family of proteins that have been implicated in variety functions including mitochondrial stress signalling and housekeeping, cell cycle progression, apoptosis, lifespan regulation many others. The human prohibitins prohibitin 1 2 proposed to act as scaffolds within the inner membrane, but their molecular organization has remained elusive. Here we determined complex membrane using an integrative structural biology approach combining quantitative western blotting, cryo-electron tomography, subtomogram averaging modelling. bell-shaped structure consists 11 alternating molecules. This study reveals average about 43 complexes per crista, covering 1–3% crista area. These findings provide basis for understanding functional contributions integrity spatial membrane.
Язык: Английский
Процитировано
4
Surfaces and Interfaces, Год журнала: 2023, Номер 44, С. 103706 - 103706
Опубликована: Дек. 3, 2023
Язык: Английский
Процитировано
40
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Фев. 15, 2024
Abstract Prohibitins are a highly conserved family of proteins that have been implicated in variety functions including mitochondrial stress signalling and housekeeping, cell cycle progression, apoptosis, lifespan regulation many others 1, 2 . The human prohibitins PHB1 PHB2 proposed to act as scaffolds within the inner membrane, but their molecular organisation remained elusive. Using an integrative structural biology approach combining quantitative Western blotting, cryo-electron tomography, subtomogram averaging modelling, we determined prohibitin complex membrane. bell-shaped structure consists eleven alternating molecules. This study reveals average about 43 complexes per crista, covering 1-3 % cristae membranes. These findings provide basis for understanding functional contributions integrity spatial
Язык: Английский
Процитировано
8
International Journal of Biological Macromolecules, Год журнала: 2024, Номер unknown, С. 136643 - 136643
Опубликована: Окт. 1, 2024
Язык: Английский
Процитировано
7
Molecular Pharmaceutics, Год журнала: 2025, Номер unknown
Опубликована: Март 26, 2025
Lipid nanoparticles (LNPs) have emerged as the premier drug delivery system for oligonucleotide vaccines and therapeutics in recent years. Despite their prosperous advancement research clinical applications, there is a significant lack of mechanistic understanding assembly lipid particles at molecular level. In our study, we utilized combination solution solid-state NMR, together with dynamics simulations, to elucidate local structures interactions chemical components across multiple motional regimes. Our results comprehensively evaluated impact formulation engineering process factors on particle formation identified interplay phospholipids (DSPC), poly(ethylene glycol) (PEG) conjugates, cholesterol governing size from structural perspective, using static 31P NMR techniques. These studies provide novel insights into properties LNP envelope membrane. Additionally, compositional distribution play critical role consequent stability potency. this intermolecular contacts among one-dimensional 1H-13C cross-polarization magic angle spinning experiments, 1H relaxation measurements, two-dimensional 1H-1H correlation methods, providing basis assembly. Interestingly, cationic ionizable lipids, conventionally regarded stabilizing agents primarily located within core LNPs, were found interact PEG lipids coexist outer layer particles. We suggest that LNPs examined here are comprised an rich surrounding region. high-resolution findings offer insightful dynamic details pertaining individual influence complex structure engineering.
Язык: Английский
Процитировано
1
Journal of Chemical Theory and Computation, Год журнала: 2023, Номер 20(4), С. 1704 - 1716
Опубликована: Сен. 7, 2023
The outer lipopolysaccharide (LPS) membrane of Gram-negative bacteria forms the main barrier for transport antimicrobial molecules into bacterial cell. In this study we develop coarse-grained models
Язык: Английский
Процитировано
14
Current Opinion in Structural Biology, Год журнала: 2024, Номер 87, С. 102837 - 102837
Опубликована: Май 13, 2024
Molecular dynamics simulations of cellular membranes have come a long way-from simple model lipid bilayers to multicomponent systems capturing the crowded and complex nature real cell membranes. In this opinionated minireview, we discuss current challenge simulate in their native environment, situ, with prospect reaching level whole cells organelles using an integrative modeling framework.
Язык: Английский
Процитировано
5
Journal of Molecular Biology, Год журнала: 2024, Номер 436(17), С. 168554 - 168554
Опубликована: Март 27, 2024
Язык: Английский
Процитировано
4