Computationally efficient approach for the identification of ice-binding surfaces and how they bind ice

Abstract

Recognition and binding of ice by proteins, crystals, and other surfaces is key for their control of the nucleation and growth of ice. Docking is the state-of-the-art computational method to identify ice-binding surfaces (IBS). However, docking methods require a priori knowledge of the ice plane to which the molecules bind and either neglect the competition of ice and water for the IBS or are computationally expensive. Here we present and validate a robust methodology for the identification of the IBS of molecules and crystals that is easy to implement and a hundred times computationally more efficient than the most advanced ice-docking approaches. The methodology is based on biased sampling with an order parameter that drives the formation of ice. We validate the method using all-atom and coarse-grained models of organic crystals and proteins. To our knowledge, this approach is the first to simultaneously identify the ice-binding surface as well as the plane of ice to which it binds, without the use of structure search algorithms. We show that biased simulations even identify surfaces that are too small or too weak to heterogeneously nucleate ice. The biasing simulations can be used to identify of IBS of antifreeze and ice nucleating proteins and to equilibrate ice seeds bound to an IBS for the calculation of heterogeneous ice nucleation rates using classical nucleation theory.

Is Ice Nucleation by Organic Crystals Nonclassical? An Assessment of the Monolayer Hypothesis of Ice Nucleation

“…Figure shows that simulations with the united atom mW and all-atom TIP4P/Ice water models predict the same order of the ITL and of interfacial water in contact with liquid water. This should not be surprising, as these water models predict the same structures and phase behavior for bulk water, ice, and hydrates ,,,− ,,, and also the same crystals and quasi-crystals for confined water in contact with other surfaces. ,, Figure details the hydrogen-bonding patterns of water and OH at the ice–organic interface in the all-atom simulation: the ITL contains five- and six-membered hydrogen-bonding rings of water and OH groups of phloroglucinol. We interpret that the exposure of hydrophobic CH groups on the surface of PD (Figure ) favors the formation of water pentagons, a signature of hydrophobic hydration previously observed in the hydration structure other organic , and biological surfaces, including the ice-binding surface of bacterial ice nucleating and antifreeze proteins. ,, …”

“…The nucleation simulations are performed by cooling mW water in contact with the (100), (001), and (010) faces of phloroglucinol dihydrate at a rate of 1 K ns –1 , the fastest cooling rate that results in ice nucleation of the water model. , The homogeneous nucleation temperature of mW at that cooling rate is T hom = 202 ± 1 K . We validate the order of interfacial water and mode of binding to ice of the united atom model of phloroglucinol and mW water with an all-atom model of phloroglucinol and TIP4P/Ice water in simulations with a harmonic restraint on the global order parameter Q 6 that bias the formation of ice . The simulations discussed below are performed with the united atom models, except when otherwise is indicated.…”

“…Performing simulations of spontaneous ice nucleation with all-atom models is, however, computationally prohibitive. Instead, we investigate the hydrogen-bonding pattern of the ordered interfacial monolayer on the (010) face of PD through the analysis of simulations from ref that bias the formation of ice through a harmonic restraint in the global order parameter Q 6 for the all-atom TIP4P/Ice water models at 260 K in contact with the (010) face of the organic crystal modeled with an all-atom model of phloroglucinol. Figure shows that simulations with the united atom mW and all-atom TIP4P/Ice water models predict the same order of the ITL and of interfacial water in contact with liquid water.…”

“…Order of interfacial water before and after ice crystallization at 260 K on the (010) face of phloroglucinol dihydrate modeled with (a) united atom models of phloroglucinol and mW water and (b) all-atom model of phloroglucinol and TIP4P/Ice water. Simulations cells of both models are from ref in cells of identical size, with an organic–water interface of ∼25 nm 2 area (about 1/4 of the ones used for spontaneous nucleation for nucleation in this study). The top panels show the structure of interfacial water (green balls) and OH groups (red balls) at the PD–water interface in the absence of a bias; the middle panels display the interfacial water on the same cells when water has been crystallized with a bias in the global order parameter Q 6 .…”

“…Preordering of interfacial water before the nucleation of ice has been reported for a large variety of ice nucleating surfaces. − Simulation studies of ice nucleation on hydroxylated inorganic substrates, such as kaolinite and alcohol monolayers, , show that interfacial water in contact with the liquid acquires a transient hexagonal pattern that resembles the one on ice faces. Preordering of water has also been found on the surface of cholesterol monohydrate, the only organic crystal studied to date in simulations of ice nucleation, , and for large assemblies of ice nucleating proteins exposing their amphiphilic ice-binding surfaces to water . Preordering of interfacial water has been shown to increase the rate of ice nucleation on graphite, although its impact was small: <1 order of magnitude .…”