Calculation of the permeability coefficients of small molecules through lipid bilayers by free-energy reaction network analysis following the explicit treatment of the internal conformation of the solute

Mitsuta, Yuki; Asada, Toshio; Shigeta, Yasuteru

doi:10.1039/d2cp03678a

Cited by 6 publications

(2 citation statements)

References 71 publications

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“…The first is a complete description of the collective variable space to describe the free energy landscapes for molecule translocation, which is more complex in the case of proteins and antimicrobial peptides. In addition to the depth of penetration, rotational degrees of freedom and secondary structure changes that occur during membrane insertion need to be included as collective variables . There is also a need to use more accurate inner membrane compositions that correspond to the bacterial membranes of Gram-positive and Gram-negative strains.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the depth of penetration, rotational degrees of freedom and secondary structure changes that occur during membrane insertion need to be included as collective variables. 190 There is also a need to use more accurate inner membrane compositions that correspond to the bacterial membranes of Gram-positive and Gram-negative strains. When secondary structure changes are involved, appropriate coarse-grained methods that reliably capture unfolding and refolding events 187,191 should be used to obtain the free energy landscape.…”

Section: ■ Conclusion and Perspectivesmentioning

confidence: 99%

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Structure of the Bacterial Cell Envelope and Interactions with Antimicrobials: Insights from Molecular Dynamics Simulations

Sharma,

Vaiwala,

Gopinath

et al. 2024

Langmuir

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Bacteria have evolved over 3 billion years, shaping our intrinsic and symbiotic coexistence with these single-celled organisms. With rising populations of drug-resistant strains, the search for novel antimicrobials is an ongoing area of research. Advances in highperformance computing platforms have led to a variety of molecular dynamics simulation strategies to study the interactions of antimicrobial molecules with different compartments of the bacterial cell envelope of both Gram-positive and Gram-negative species. In this review, we begin with a detailed description of the structural aspects of the bacterial cell envelope. Simulations concerned with the transport and associated free energy of small molecules and ions through the outer membrane, peptidoglycan, inner membrane and outer membrane porins are discussed. Since surfactants are widely used as antimicrobials, a section is devoted to the interactions of surfactants with the cell wall and inner membranes. The review ends with a discussion on antimicrobial peptides and the insights gained from the molecular simulations on the free energy of translocation. Challenges involved in developing accurate molecular models and coarse-grained strategies that provide a trade-off between atomic details with a gain in sampling time are highlighted. The need for efficient sampling strategies to obtain accurate free energies of translocation is also discussed. Molecular dynamics simulations have evolved as a powerful tool that can potentially be used to design and develop novel antimicrobials and strategies to effectively treat bacterial infections.

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Section: Discussionmentioning

confidence: 99%

Section: ■ Conclusion and Perspectivesmentioning

confidence: 99%

Structure of the Bacterial Cell Envelope and Interactions with Antimicrobials: Insights from Molecular Dynamics Simulations

Sharma,

Vaiwala,

Gopinath

et al. 2024

Langmuir

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Water–triglyceride interfaces limit permeability and diffusion of aroma molecules in butter

Koch,

Briesen

2024

Euro J Lipid Sci & Tech

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Insight into the dynamics of aroma molecules in bulk phases and at water–triglyceride interfaces is crucial for elucidating the aroma release mechanisms in complex dairy products such as butter. This study employs classical, all‐atom molecular dynamics simulations with umbrella sampling to investigate the energetics and kinetics of key aroma‐active compounds, including diacetyl, ‐decalactone, and butyric acid, at interfaces of 1,3‐dipalmitoyl‐2‐oleoylglycerol (POP) in water. The chemical properties of aroma compounds, including polarity, hydrogen bonding, and van der Waals interactions, play a pivotal role in their interaction with interfacial molecules, resulting in unique profiles of the potential of mean force and diffusivity. In particular, ‐decalactone preferentially resides at the interface and accumulates in the triglyceride phase. Aroma permeability through the complexly organized water–triglyceride interface significantly decreases from ‐decalactone to butyric acid, with a less pronounced reduction for diacetyl. Surprisingly, this trend in aroma permeability at interfaces does not coincide with trends in aroma diffusion within both pure bulk phases. This discrepancy is attributed to local, heterogeneous molecular structuring at water–triglyceride interfaces, impeding the interfacial permeation processes and leading to local aroma confinement.Practical Application: Employing a water–POP interface as a case study, the methodology investigates aroma compound diffusion within bulk phases, delineating limitations in aroma permeability in dairy products with extended water–triglyceride interfaces. This is a substep in the aroma release process, contributing to the interpretation of perception studies by sensory panels in human sensory experiments and fostering a deeper understanding of the intricate dynamics inherent to individual compounds.

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Permeability of TB drugs through the mycolic acid monolayer: a tale of two force fields

Basu,

Mandal,

Maiti

2024

Phys. Chem. Chem. Phys.

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Calculation of the permeability coefficients of small molecules through lipid bilayers by free-energy reaction network analysis following the explicit treatment of the internal conformation of the solute

Abstract: Biomembrane permeation represents a major barrier to pharmacokinetics. During preclinical drug discovery, the coefficients of the permeation of molecules through lipid bilayers account for a valuable property of such molecules....

Cited by 6 publications

References 71 publications

Structure of the Bacterial Cell Envelope and Interactions with Antimicrobials: Insights from Molecular Dynamics Simulations

Structure of the Bacterial Cell Envelope and Interactions with Antimicrobials: Insights from Molecular Dynamics Simulations

Water–triglyceride interfaces limit permeability and diffusion of aroma molecules in butter

Permeability of TB drugs through the mycolic acid monolayer: a tale of two force fields

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