A1 Journal article (refereed)
Scalable Constant pH Molecular Dynamics in GROMACS (2022)

Aho, N., Buslaev, P., Jansen, A., Bauer, P., Groenhof, G., & Hess, B. (2022). Scalable Constant pH Molecular Dynamics in GROMACS. Journal of Chemical Theory and Computation, 18(10), 6148-6160. https://doi.org/10.1021/acs.jctc.2c00516

JYU authors or editors

Publication details

All authors or editorsAho, Noora; Buslaev, Pavel; Jansen, Anton; Bauer, Paul; Groenhof, Gerrit; Hess, Berk

Journal or seriesJournal of Chemical Theory and Computation



Publication year2022

Publication date21/09/2022


Issue number10

Pages range6148-6160

PublisherAmerican Chemical Society (ACS)

Publication countryUnited States

Publication languageEnglish


Publication open accessOpenly available

Publication channel open access

Publication is parallel published (JYX)https://jyx.jyu.fi/handle/123456789/83385


Molecular dynamics (MD) computer simulations are used routinely to compute atomistic trajectories of complex systems. Systems are simulated in various ensembles, depending on the experimental conditions one aims to mimic. While constant energy, temperature, volume, and pressure are rather straightforward to model, pH, which is an equally important parameter in experiments, is more difficult to account for in simulations. Although a constant pH algorithm based on the λ-dynamics approach by Brooks and co-workers [Kong, X.; Brooks III, C. L. J. Chem. Phys.1996, 105, 2414–2423] was implemented in a fork of the GROMACS molecular dynamics program, uptake has been rather limited, presumably due to the poor scaling of that code with respect to the number of titratable sites. To overcome this limitation, we implemented an alternative scheme for interpolating the Hamiltonians of the protonation states that makes the constant pH molecular dynamics simulations almost as fast as a normal MD simulation with GROMACS. In addition, we implemented a simpler scheme, called multisite representation, for modeling side chains with multiple titratable sites, such as imidazole rings. This scheme, which is based on constraining the sum of the λ-coordinates, not only reduces the complexity associated with parametrizing the intramolecular interactions between the sites but also is easily extendable to other molecules with multiple titratable sites. With the combination of a more efficient interpolation scheme and multisite representation of titratable groups, we anticipate a rapid uptake of constant pH molecular dynamics simulations within the GROMACS user community.

Keywordsmolecular dynamicsmoleculespeptidesproteinspotential energyreaction mechanisms

Free keywordsmolecular mechanics; monomers; peptides and proteins; potential energy; reaction mechanisms

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Ministry reportingYes

Reporting Year2022

JUFO rating2

Last updated on 2024-03-04 at 21:46