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Direct mixing of atomistic solutes and coarse-grained water

Orsi, Mario; Ding, Wei; Palaiokostas, Michail

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Mario Orsi
Senior Lecturer in Maths Supporting Science

Wei Ding

Michail Palaiokostas


© 2014 American Chemical Society. We present a new dual-resolution approach for coupling atomistic and coarse-grained models in molecular dynamics simulations of hydrated systems. In particular, a coarse-grained point dipolar water model is used to solvate molecules represented with standard all-atom force fields. A unique characteristic of our methodology is that the mixing of resolutions is direct, meaning that no additional or ad hoc scaling factors, intermediate regions, or extra sites are required. To validate the methodology, we compute the hydration free energy of 14 atomistic small molecules (analogs of amino acid side chains) solvated by the coarse-grained water. Remarkably, our predictions reproduce the experimental data as accurately as the predictions from state-of-the-art fully atomistic simulations. We also show that the hydration free energy of the coarse-grained water itself is in comparable or better agreement with the experimental value than the predictions from all but one of the most common multisite atomistic models. The coarse-grained water is then applied to solvate a typical atomistic protein containing both α-helix and β-strand elements. Moreover, parallel tempering simulations are performed to investigate the folding free energy landscape of a representative α helical and a β hairpin structure. For the simulations considered in this work, our dual-resolution method is found to be 3 to 6 times more computationally efficient than corresponding fully atomistic approaches.


Orsi, M., Ding, W., & Palaiokostas, M. (2014). Direct mixing of atomistic solutes and coarse-grained water. Journal of Chemical Theory and Computation, 10(10), 4684-4693.

Journal Article Type Article
Acceptance Date Aug 27, 2014
Publication Date Oct 14, 2014
Deposit Date Sep 26, 2016
Publicly Available Date Sep 26, 2016
Journal Journal of Chemical Theory and Computation
Print ISSN 1549-9618
Electronic ISSN 1549-9626
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 10
Issue 10
Pages 4684-4693
Public URL
Publisher URL
Additional Information Additional Information : The final publication is available at


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