100th Anniversary of Macromolecular Science Viewpoint: Modeling and Simulation of Macromolecules with Hydrogen Bonds: Challenges, Successes, and Opportunities

Macromolecular materials with directional interactions such as hydrogen bonds exhibit numerous attractive features in terms of structure, thermodynamics, and dynamics. Besides enabling precise tuning of desirable geometries in the assembled state (e.g., programmable coordination numbers depending on the valency of the directional interaction), mixing in a blend/composite through stabilization via hydrogen bonds between the various components, hydrogen bonds can also impart responsiveness to external stimuli (e.g., temperature, pH). In biomacromolecules (e.g., proteins, DNA, polysaccharides), hydrogen bonds play a key role in stabilizing secondary and tertiary structures, which in turn define the function of these macromolecules. In this Viewpoint, I present the challenges, successes, and opportunities for molecular modeling and simulations to conduct fundamental and application-focused research on macromolecular materials with hydrogen bonding interactions. The past successes and limitations of atomistic simulations are discussed first, followed by highlights from recent developments in coarse-grained modeling and their use in studies of (synthetic and biologically relevant) macromolecular materials. Model development focused on polynucleotides (e.g., DNA, RNA, etc.), polypeptides, polysaccharides, and synthetic polymers at experimentally relevant conditions are highlighted. This viewpoint ends with potential future directions for macromolecular modeling and simulations with other types of directional interactions beyond hydrogen bonding.