Enhancing MM/P(G)BSA Methods : Integration of Formulaic Entropy for Improved Binding Free Energy Calculations

© 2025 Wiley Periodicals LLC.

Bibliographische Detailangaben
Veröffentlicht in:Journal of computational chemistry. - 1984. - 46(2025), 10 vom: 15. Apr., Seite e70093
1. Verfasser: Dong, Lina (VerfasserIn)
Weitere Verfasser: Li, Pengfei, Wang, Binju
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2025
Zugriff auf das übergeordnete Werk:Journal of computational chemistry
Schlagworte:Journal Article MM/GBSA MM/PBSA binding free energy entropy virtual screening
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520 |a Balancing computational efficiency and precision, MM/P(G)BSA methods have been widely employed in the estimation of binding free energies within biological systems. However, the entropy contribution to the binding free energy is often neglected in MM/P(G)BSA calculations, due to the computational cost of conventional methods such as normal mode analysis (NMA). In this work, the entropy effect using a formulaic entropy can be computed from one single structure according to variations in the polar and non-polar solvents accessible surface areas and the count of rotatable bonds in ligands. It was incorporated into MM/P(G)BSA methods to enhance their performance. Extensive benchmarking reveals that the integration of formulaic entropy systematically elevates the performance of both MM/PBSA and MM/GBSA without incurring additional computational expenses. In addition, we found the inclusion of dispersion can deteriorate the correlation performance (Rp) but reduce the root mean square error (RMSE) of both MM/PBSA and MM/GBSA. Notably, MM/PBSA_S, including the formulaic entropy but excluding the dispersion, surpasses all other MM/P(G)BSA methods across a spectrum of datasets. Our investigation furnishes a valuable and practical MM/P(G)BSA method, optimizing binding free energy calculations for a variety of biological systems 
650 4 |a Journal Article 
650 4 |a MM/GBSA 
650 4 |a MM/PBSA 
650 4 |a binding free energy 
650 4 |a entropy 
650 4 |a virtual screening 
700 1 |a Li, Pengfei  |e verfasserin  |4 aut 
700 1 |a Wang, Binju  |e verfasserin  |4 aut 
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