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

Abstract

Hybrid all-atom/coarse-grained (AA-CG) simulations in which AA solutes are embedded in a CG environment can provide a significant computational speed-up over conventional fully atomistic simulations and thus alleviate the current length and time scale limitations of molecular dynamics (MD) simulations of large biomolecular systems. On one hand, coarse graining the solvent is particularly appealing, since it typically constitutes the largest part of the simulation system and thus dominates computational cost. On the other hand, retaining atomic-level solvent layers around the solute is desirable for a realistic description of hydrogen bonds and other local solvation effects. Here, we devise and systematically validate fixed resolution AA-CG schemes, both with and without atomistic water layers. To quantify the accuracy and diagnose possible pitfalls, Gibbs free energies of solvation of amino acid side chain analogues were calculated, and the influence of the nature of the CG solvent surrounding (polarizable vs nonpolarizable CG water) and the size of the AA solvent region was investigated. We show that distance restraints to keep the AA solvent around the solute lead to too high of a density in the inner shell. Together with a long-ranged effect due to orientational ordering of water molecules at the AA-CG boundary, this affects solvation free energies. Shifting the onset of the distance restraints slightly away from the central solute significantly improves solvation free energies, down to mean unsigned errors with respect to experiment of 2.3 and 2.6 kJ/mol for the polarizable and nonpolarizable CG water surrounding, respectively. The speed-up of the nonpolarizable model renders it computationally more attractive. The present work thus highlights challenges, and outlines possible solutions, involved with modeling the boundary between different levels of resolution in hybrid AA-CG simulations.

Thermodynamics of adaptive molecular resolution

“…Then, the TD force was set to −dμ ex /dx, which in our terminology implies dF = −dμ ex . Decomposingμ into ideal and excess parts,μ = k B T ln[nΛ 3 ] +μ ex (with Λ the de Broglie thermal wavelength) and using equation (2.13),…”

“…In particular, the adaptive resolution simulation (AdResS) method introduced by Praprotnik et al [1] is the subject of the present discussion. The idea of adaptive resolution is certainly attractive for multiscale modelling: a finely detailed model (atomistic) is used to resolve some (small) location of the simulation box, whereas molecules gradually lose or gain atomistic details as they cross towards or backwards from the outer coarse-grained ( and contributions from several groups [3][4][5][6][7] and has been generalized in several directions, such as coupling AdResS with continuum hydrodynamics [8,9], using open molecular dynamics (MD) [10], polarizable water models [11] and more. The main idea of AMR is to reduce the computational burden outside the domain of interest (e.g.…”

Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology

“…Hybrid multiscale simulations in which portions of the system are represented at CG resolution while other parts are described at a fine-grain resolution have also been reported (Genheden and Essex 2015 ; Kar and Feig 2017 ; Kuhn et al. 2015 ). Bioinformatics methods such as prediction of transmembrane regions of membrane proteins and phylogenetic studies provide an important complement to simulation studies, in particular when structures are either incomplete or not available at all (Tian et al.…”

Hydration Properties and Solvent Effects for All-Atom Solutes in Polarizable Coarse-Grained Water

“…17 In addition, using the GROMOS polarizable CG water model, Kuhn et al reported an MUE of 1.96 kcal/mol for 12 side-chain analogues, with less negative calculated free energy values for strongly polar side chains and more negative values for non-polar ones. 18 …”