The Effects of Conformational Sampling and QM Region Size in QM/MM Simulations: An Adaptive QM/MM Study With Model Systems

Paz H, Beck S, Lee R, Ho J, Yu H (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Journal of Computational Chemistry Wiley-Blackwell

Book Volume: 46

Pages Range: e70109-

Journal Issue: 11

DOI: 10.1002/jcc.70109

Abstract

Molecular properties in combined quantum mechanics and molecular mechanics (QM/MM) simulations have been shown to be dependent on the size of the quantum mechanical (QM) region and the amount of conformational sampling. Previous studies have largely focused on enzymatic systems, which have made it difficult to distinguish the effects of QM region size and conformational sampling from other factors including QM-MM boundary artifacts and the boundary effects. This study uses the difference-based adaptive solvation QM/MM method to investigate the tautomerization reactions of alanine and aspartate in explicit solvent. The choice of computationally tractable systems enables the decoupling of QM region size effects from other factors and a direct comparison of free energy surfaces with potential energy surfaces (PESs). The results show that (1) it is crucial to properly account for thermal fluctuations along the reaction pathways, and (2) free energy surfaces converge rapidly with increasing QM region size, whereas charge transfer requires a slightly larger QM region to achieve convergence. These findings are expected to guide future studies of enzymatic systems and other complex systems where QM/MM methods are applied.

Authors with CRIS profile

Silvan Beck Lehrstuhl für Biochemie und Molekulare Medizin

Involved external institutions

University of Wollongong (UOW) AU Australia (AU) University of New South Wales (UNSW) AU Australia (AU)

How to cite

APA:

Paz, H., Beck, S., Lee, R., Ho, J., & Yu, H. (2025). The Effects of Conformational Sampling and QM Region Size in QM/MM Simulations: An Adaptive QM/MM Study With Model Systems. Journal of Computational Chemistry, 46(11), e70109-. https://doi.org/10.1002/jcc.70109

MLA:

Paz, Holden, et al. "The Effects of Conformational Sampling and QM Region Size in QM/MM Simulations: An Adaptive QM/MM Study With Model Systems." Journal of Computational Chemistry 46.11 (2025): e70109-.

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