Hybrid simulations of atomistic (AA) solutes embedded in coarse-grained (CG) environment can substantially reduce the computational cost with respect to fully atomistic representations. However, interfacing both levels of resolution is a major challenge that requires a balanced description of all relevant interactions. We introduced and critically tested computationally efficient hybrid AA/CG models that contain explicit electrostatic coupling between the two regimes. This coupling is particularly important for polar solvents such as water that screen the electrostatic interactions. Results from hybrid simulations in which different parameter sets of the Gromos atomistic force field were combined with the Martini coarse-grained force field are presented. However, the introduced coupling scheme is modular and general and can thus readily be extended to other force field combinations as well. To enact electrostatic coupling, various recently developed polarizable CG water models were used. The hybrid model was found to be highly sensitive to the strength of the AA/CG electrostatic coupling, which was adjusted through the relative dielectric permittivity er(AA�CG). Potentials of mean force (PMFs) between pairs of amino acid side chains in water, and partitioning free enthalpies of uncharged amino acid side chains between apolar solvent and water obtained from hybrid AA/CG simulations are systematically compared to the respective data from fully AA or fully CG simulations. Finally, the structure and dynamics of small atomistic proteins in CG water and of atomistic membrane proteins embedded in solvated CG lipid bilayers are analyzed and critically discussed in terms of the observed overstabilization of intra-protein interactions. This work highlights some key challenges and suggests possible solutions on the way toward hybrid AA/CG models that are both computationally efficient and at the same time sufficiently accurate to address biomolecular systems.

On electrostatic coupling in hybrid all-atom/coarse-grained biomolecular simulations

246th National Meeting (2013)

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