Electronic polarization effects on membrane translocation of anti-cancer drugs
Najla Hosseini, Atiyeh ; Lund, Mikael LU
and Ejtehadi, Mohammad Reza
(2022)
In Physical Chemistry Chemical Physics
24(20).
p.12281-12292
- Abstract
Free-energy calculations are crucial for investigating biomolecular interactions. However, in theoretical studies, the neglect of electronic polarization can reduce predictive capabilities, specifically for free-energy calculations. To effectively mimick polarization, we explore a Charge Switching (CS) model, aiming to narrow the gap between computational and experimental results. The model requires quantum-level partial charge calculations of the molecule in different environments, combined with atomistic MD simulations. Studying three different anti-cancer drug molecules with three different phospholipid membranes, we show that the method significantly improves agreement with available experimental data. In contrast, using... (More)
Free-energy calculations are crucial for investigating biomolecular interactions. However, in theoretical studies, the neglect of electronic polarization can reduce predictive capabilities, specifically for free-energy calculations. To effectively mimick polarization, we explore a Charge Switching (CS) model, aiming to narrow the gap between computational and experimental results. The model requires quantum-level partial charge calculations of the molecule in different environments, combined with atomistic MD simulations. Studying three different anti-cancer drug molecules with three different phospholipid membranes, we show that the method significantly improves agreement with available experimental data. In contrast, using conventional fixed charge atomistic methods, qualitative discrepancies with experiments are observed, and we show that neglecting polarization may lead to an unphysical free energy sign inversion. While the CS method is here applied to anti-cancer drug-membrane translocation, it could be used more generally to study processes considering solvent effects.
(Less)
- author
- Najla Hosseini, Atiyeh
; Lund, Mikael
LU
and Ejtehadi, Mohammad Reza
- organization
- publishing date
- 2022-04-18
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Physical Chemistry Chemical Physics
- volume
- 24
- issue
- 20
- pages
- 12 pages
- publisher
- Royal Society of Chemistry
- external identifiers
-
- scopus:85131432801
- pmid:35543365
- ISSN
- 1463-9076
- DOI
- 10.1039/d2cp00056c
- language
- English
- LU publication?
- yes
- id
- 460a18e2-6f53-4fea-93e5-d96d1e970367
- date added to LUP
- 2022-08-18 14:24:30
- date last changed
- 2024-06-26 05:59:39
@article{460a18e2-6f53-4fea-93e5-d96d1e970367,
abstract = {{<p>Free-energy calculations are crucial for investigating biomolecular interactions. However, in theoretical studies, the neglect of electronic polarization can reduce predictive capabilities, specifically for free-energy calculations. To effectively mimick polarization, we explore a Charge Switching (CS) model, aiming to narrow the gap between computational and experimental results. The model requires quantum-level partial charge calculations of the molecule in different environments, combined with atomistic MD simulations. Studying three different anti-cancer drug molecules with three different phospholipid membranes, we show that the method significantly improves agreement with available experimental data. In contrast, using conventional fixed charge atomistic methods, qualitative discrepancies with experiments are observed, and we show that neglecting polarization may lead to an unphysical free energy sign inversion. While the CS method is here applied to anti-cancer drug-membrane translocation, it could be used more generally to study processes considering solvent effects.</p>}},
author = {{Najla Hosseini, Atiyeh and Lund, Mikael and Ejtehadi, Mohammad Reza}},
issn = {{1463-9076}},
language = {{eng}},
month = {{04}},
number = {{20}},
pages = {{12281--12292}},
publisher = {{Royal Society of Chemistry}},
series = {{Physical Chemistry Chemical Physics}},
title = {{Electronic polarization effects on membrane translocation of anti-cancer drugs}},
url = {{http://dx.doi.org/10.1039/d2cp00056c}},
doi = {{10.1039/d2cp00056c}},
volume = {{24}},
year = {{2022}},
}