We provide a molecular-level description of the thermodynamics and mechanistic aspects of drug permeation through the cell membrane. As a case study, we considered the antimalaria FDA approved drug chloroquine. Molecular dynamics simulations of the molecule (in its neutral and protonated form) were performed in the presence of different lipid bilayers, with the aim of uncovering key aspects of the permeation process, a fundamental step for the drug’s action. Free energy values obtained by well-tempered metadynamics simulations suggest that the neutral form is the only permeating protomer, consistent with experimental data. H-bond interactions of the drug with water molecules and membrane headgroups play a crucial role for permeation. The presence of the transmembrane potential, investigated here for the first time in a drug permeation study, does not qualitatively affect these conclusions.

Physical Chemistry of Chloroquine Permeation through the Cell Membrane with Atomistic Detail / Paulikat, M.; Piccini, G.; Ippoliti, E.; Rossetti, G.; Arnesano, F.; Carloni, P.. - In: JOURNAL OF CHEMICAL INFORMATION AND MODELING. - ISSN 1549-9596. - 63:22(2023), pp. 7124-7132. [10.1021/acs.jcim.3c01363]

Physical Chemistry of Chloroquine Permeation through the Cell Membrane with Atomistic Detail

Piccini G.;
2023

Abstract

We provide a molecular-level description of the thermodynamics and mechanistic aspects of drug permeation through the cell membrane. As a case study, we considered the antimalaria FDA approved drug chloroquine. Molecular dynamics simulations of the molecule (in its neutral and protonated form) were performed in the presence of different lipid bilayers, with the aim of uncovering key aspects of the permeation process, a fundamental step for the drug’s action. Free energy values obtained by well-tempered metadynamics simulations suggest that the neutral form is the only permeating protomer, consistent with experimental data. H-bond interactions of the drug with water molecules and membrane headgroups play a crucial role for permeation. The presence of the transmembrane potential, investigated here for the first time in a drug permeation study, does not qualitatively affect these conclusions.
2023
63
22
7124
7132
Physical Chemistry of Chloroquine Permeation through the Cell Membrane with Atomistic Detail / Paulikat, M.; Piccini, G.; Ippoliti, E.; Rossetti, G.; Arnesano, F.; Carloni, P.. - In: JOURNAL OF CHEMICAL INFORMATION AND MODELING. - ISSN 1549-9596. - 63:22(2023), pp. 7124-7132. [10.1021/acs.jcim.3c01363]
Paulikat, M.; Piccini, G.; Ippoliti, E.; Rossetti, G.; Arnesano, F.; Carloni, P.
File in questo prodotto:
File Dimensione Formato  
paulikat-et-al-2023-physical-chemistry-of-chloroquine-permeation-through-the-cell-membrane-with-atomistic-detail.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 6.01 MB
Formato Adobe PDF
6.01 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1330534
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact