Computer Simulation of Water Sorption on Flexible Protein Crystals

Abstract

The first simulation study of water sorption on a flexible protein crystal is presented, along with a new computational approach for calculating sorption isotherms on compliant materials. The flexible ubiquitin crystal examined in the study exhibits appreciable sorption-induced swelling during fluid uptake, similar to that reported in experiments on protein powders. A completely rigid ubiquitin crystal is also examined to investigate the impact that this swelling behavior has on water sorption. The water isotherms for the flexible crystal exhibit Type II-like behavior with sorption hysteresis, which is consistent with experimental measurements on protein powders. Both of these behaviors, however, are absent in the rigid crystal, indicating that modeling flexibility is crucial for predicting water sorption behavior in protein systems. Changes in the enthalpy of adsorption, specific volume, and internal protein fluctuations that occur during sorption in the flexible crystal are also shown to compare favorably with experiment.

Effects of disulfide bridges and backbone connectivity on water sorption by protein matrices

“…Palmer et al . previously showed, using ubiquitin as a model system, that hysteresis disappears when this protein is treated as perfectly rigid at its fully hydrated structure 19 . That study, along with the present observation of reduction of hysteresis in the presence of disulfide linkages, suggests a close connection between rigidity of proteins and shrinkage of hysteresis between the adsorption and desorption isotherms.…”

“…These intrinsic factors could, for example, influence the accessibility of hydrophilic residues to the water molecules, thereby altering protein-water interactions 12 – 18 . Recently, it has been shown computationally that water sorption isotherms are significantly affected when a protein’s flexibility 19 , 20 and its fraction of charged amino acids 21 are altered. However, despite numerous water sorption studies, and the well-known fact that most globular proteins and protein products at ambient conditions exhibit a generic sigmoidal water sorption isotherm (type II in IUPAC convention 22 ) with a pronounced hysteresis between adsorption and desorption branches, the effects of the above-mentioned intrinsic factors on water sorption behavior have not been studied systematically, and hence remain poorly understood.…”

“…A major challenge in gaining fundamental understanding of water sorption isotherms lies in the lack of appropriate spatio-temporal resolution in experiments, and, until recently, in the comparative lack of computational methods that are adequate for simulating the isotherms 19 , 23 . Previously, hybrid techniques that combine molecular dynamics (MD) and grand canonical Monte Carlo (GCMC) have been used to simulate sorption isotherms of flexible adsorbents, but it has been challenging to ensure proper homogenization of MD and GCMC, which is essential for microscopic reversibility, and to attain satisfactory computational efficiency 19 , 24 , 25 . Recent advances in simulation methods 23 , however, have enabled the efficient simulation of water sorption isotherms of flexible protein matrices using an exclusively MD-based approach.…”

Molecular simulation of capillary phase transitions in flexible porous materials

“…Even with simplified models of flexible adsorbents, conventional brute-force simulation methods are inadequate for traversing the rugged free energy landscapes in these systems. Specialized hybrid methods combining the benefits of molecular dynamics and Monte Carlo have been developed to address this problem, [43][44][45][46][47][48] but they still struggle to surmount the large free energy barriers associated with phase transitions. Recently, flat-histogram sampling methods have been used to construct the free energy landscape for fluids adsorbed in flexible slit pores, thus providing a comprehensive description of their equilibrium thermodynamics.…”

Recent advances in molecular simulation: A chemical engineering perspective

“…Less than 3 decades ago, the state of the art was embodied by the first direct simulations of phase equilibria for simple fluids such as argon . Today, chemical engineers routinely apply molecular simulation to study challenging problems related to drug design and formulation; biomolecular crowding; protein folding and aggregation; wetting phenomena and hydration thermodynamics; nucleation and growth processes; the thermophysical properties of complex fluids such as ionic liquids and liquid crystals; the phase behavior of polymeric, colloidal, and self‐assembled systems; and the synthesis, design and characterization of advanced materials for applications ranging from adsorption‐separation processes to energy conversion and storage …”