Direct Mixing of Atomistic Solutes and Coarse-Grained Water

Abstract

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.

Adaptive resolution simulation of polarizable supramolecular coarse-grained water models

“…The emerging multiscale simulation methods 12,[15][16][17][18][19][20] are the optimal way to tackle such situations as they bypass the trade-off between accuracy and efficiency of a model. The adaptive resolution scheme (AdResS) is such a method and allows one to simulate a system at multiple resolutions.…”

On Using Atomistic Solvent Layers in Hybrid All-Atom/Coarse-Grained Molecular Dynamics Simulations

“…[11][12][13] In this latter approach of Essex and coworkers, additional system-dependent scaling parameters had to be introduced. This limitation is overcome in the recent AA/CG scheme of Orsi and coworkers, 14 which is based on the ELBA CG water model. 15,16 In all the above AA/CG schemes, CG water models in which a single atomistic water molecule is mapped to a single CG molecule were applied, thus limiting the achievable computational speed-up.…”

All-atom/coarse-grained hybrid predictions of distribution coefficients in SAMPL5

“…Our methodology is simple and efficient: we approximate the distribution coefficient by the partition coefficient through the estimation of solvation free energies in water and cyclohexane, employing a hybrid all-atom/coarse-grained model. Such an approach is at least ten times faster than a corresponding all-atom approach [21, 22]; a solvation free energy in water and cyclohexane is computed in 13 and 7 CPU hours on average, respectively on 12 cores of a Cray XC30 machine. We have previously used this hybrid model to produce hexane/water and octanol/water predictions with high accuracy both in comparison to experiment and to a more expensive all-atom solvent model [23].…”

“…solvent molecules, are described with a CG model [21]. This model has been used to study small molecules and proteins in water and membrane environments [21, 22]. It has also been used to estimate water/hexane and water/octanol partition coefficients [23].…”