Flexible framework of computing binding free energy using the energy representation theory of solution

Okita, Kazuya; Maruyama, Yusei; Kasahara, Kento et al.

Journal of Chemical Physics, 2025, 162(3), 034103

Number of Access:469（2025-08-29 00:56 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/99615

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Title
Flexible framework of computing binding free energy using the energy representation theory of solution
Creator
CreatorName
Okita, Kazuya
CreatorName
Maruyama, Yusei
NRID
1000010824469 1000010824469
ORCID
0000-0001-7138-250X 0000-0001-7138-250X
researchmap permalink
kasakento kasakento
Scopus Author ID
56245700800 56245700800
CreatorName
Kasahara, Kento
NRID
1000020281107 1000020281107
ORCID
0000-0001-7176-441X 0000-0001-7176-441X
researchmap permalink
nbyk_MTBYS nbyk_MTBYS
Scopus Author ID
7003410578 7003410578
CreatorName
Matubayasi, Nobuyuki
Description
Okita Kazuya et al., J. Chem. Phys. 162, 034103 (2025) https://doi.org/10.1063/5.0242641.
Abstract
Host–guest binding plays a crucial role in the functionality of various systems, and its efficiency is often quantified using the binding free energy, which represents the free-energy difference between the bound and dissociated states. Here, we propose a methodology to compute the binding free energy based on the energy representation (ER) theory of solution, which enables us to evaluate the free-energy difference between the systems of interest with the molecular dynamics (MD) simulations. Unlike the other free-energy methods, such as the Bennett acceptance ratio (BAR), the ER theory does not require the MD simulations for hypothetical intermediate states connecting the systems of interest, leading to reduced computational costs. By constructing the thermodynamic cycle of the binding process that is suitable for the ER theory, a robust calculation of the binding free energy is realized. We apply the present method to the self-association of N-methylacetamide in different solvents and the binding of aspirin to β-cyclodextrin (CD) in water. In the former case, the present method estimates that the binding free energy decreases as the solvent polarity decreases. This trend is consistent with the experimental finding. For the latter system, the binding free energies for the two representative CD–aspirin bound complexes, primary (P) and secondary (S) complexes, are estimated to be −5.2 ± 0.1 and −5.03 ± 0.09 kcal mol−1, respectively. These values are satisfactorily close to those from the BAR method [−4.2 ± 0.2 and −4.1 ± 0.2 kcal mol−1 for P and S, respectively]. Furthermore, the interaction-energy component analysis reveals that the van der Waals interaction between aspirin and CD dominantly contributes to the stabilization of the bound complexes, which is in harmony with the well-known binding mechanism in the CD systems.
Publisher
AIP Publishing
Source Title
Journal of Chemical Physics
Volume (Issue)
162(3)
Page
034103
Date of Issued
2025-01-15
Language
English
Handle URL
https://hdl.handle.net/11094/99615
PISSN
00219606
eISSN
10897690
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1063/5.0242641
Access Rights
embargoed access
CopyRight
This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in Okita Kazuya et al., J. Chem. Phys. 15 January 2025; 162(3): 034103 and may be found at https://doi.org/10.1063/5.0242641.
The full-text file will be made open to the public on 15 January 2026 in accordance with the publisher's policy.
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Category
学術雑誌論文 Journal Article