Ultra-Coarse-Grained Liquid State Models with Implicit Hydrogen Bonding

J Chem Theory Comput. 2018 Dec 11;14(12):6159-6174. doi: 10.1021/acs.jctc.8b00812. Epub 2018 Nov 16.


Coarse-graining (CG) methodologies have been widely used to extend the time and length scales of computer simulations by averaging over the atomistic details beneath the resolution of the CG models. Despite the efficiency of CG models, important configurational information during a given process may be lost at the CG resolution. One example of this is the topology of the hydrogen bonding network in the liquid state. When the functional group that participates in hydrogen bonding (e.g., -OH in methanol) is coarse-grained into one CG site, the effective interactions of the resultant CG model are usually derived from an averaged overall trajectory and, thus, do not take into account the hydrogen bonding interactions and topologies that are present at the all-atom resolution. In order to overcome this challenge, the present study develops new ultra-coarse-grained (UCG) models that include internal states within the CG sites that participate in hydrogen bonding, where each state represents a specific configuration such as the hydrogen bonding donor or acceptor. Internal states of the UCG beads are modeled to remain in quasi-equilibrium, and the degree of mixing is controlled by utilizing the effective local density of the UCG sites. In particular, we consider two groups of UCG models with different types of hydrogen bonding motifs: chain-like and ring-like. Using five different liquid systems that contain the same fundamental functional groups as biomolecules, we demonstrate the ability of the UCG models to reproduce the structural properties that originate from the configurations beneath the resolution of the UCG model. This proposed approach can also be applied to other liquids with such specific and directional interactions, or even to complex biomolecular systems in which hydrogen bonding is critical.

MeSH terms

  • Hydrogen Bonding
  • Models, Molecular*
  • Molecular Conformation
  • Organic Chemicals / chemistry


  • Organic Chemicals