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

Okita, Kazuya; Maruyama, Yusei; Kasahara, Kento; Matubayasi, Nobuyuki

doi:https://doi.org/10.1063/5.0242641

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

アクセス数:23件（2025-04-05 00:17 集計）

固定URL: https://hdl.handle.net/11094/99615

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タイトル	Flexible framework of computing binding free energy using the energy representation theory of solution
著者	著者名 Okita, Kazuya
	著者名 Maruyama, Yusei
	NRID 1000010824469 1000010824469 ORCID 0000-0001-7138-250X 0000-0001-7138-250X researchmap permalink kasakento kasakento Scopus Author ID 56245700800 56245700800 著者名 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 著者名 Matubayasi, Nobuyuki
内容	Okita Kazuya et al., J. Chem. Phys. 162, 034103 (2025) https://doi.org/10.1063/5.0242641.
抄録	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.
出版者	AIP Publishing
収録物名	Journal of Chemical Physics
巻(号)	162(3)
ページ	034103
刊行年月	2025-01-15
言語	英語
ハンドルURL	https://hdl.handle.net/11094/99615
PISSN	00219606
eISSN	10897690
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1063/5.0242641
アクセス権	embargoed access
権利情報	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.
権利情報	The full-text file will be made open to the public on 15 January 2026 in accordance with the publisher's policy.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Journal of Chemical Physics. 2025, 162(3), p. 034103
DC.title	Flexible framework of computing binding free energy using the energy representation theory of solution
DC.creator	Okita, Kazuya
	Maruyama, Yusei
	Kasahara, Kento
	Matubayasi, Nobuyuki
DC.publisher	AIP Publishing
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-01-15
DC.identifier	https://doi.org/10.1063/5.0242641
DC.description	Okita Kazuya et al., J. Chem. Phys. 162, 034103 (2025) https://doi.org/10.1063/5.0242641.
DCTERMS.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.
DC.rights	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.
DC.rights	The full-text file will be made open to the public on 15 January 2026 in accordance with the publisher's policy.
DC.format	99615
citation_title	Flexible framework of computing binding free energy using the energy representation theory of solution
citation_author	Okita, Kazuya
	Maruyama, Yusei
	Kasahara, Kento
	Matubayasi, Nobuyuki
citation_publisher	AIP Publishing
citation_language	英語
citation_date	2025-01-15
citation_journal_title	Journal of Chemical Physics
citation_volume	162
citation_issue	3
citation_firstpage	034103
citation_doi	https://doi.org/10.1063/5.0242641
citation_public_url	https://hdl.handle.net/11094/99615

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

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