Molecular simulation of adsorption and its implications to protein chromatography: A review

Adsorption on solid surface is of fundamental importance in the research and development of chromatographic science and technology. Due to the limitation of the currently available experimental approaches, molecular simulation, a research tool with sufficiently small scales in both time and space, has been used to explore the molecular insights into adsorption phenomena. This article offers an overview of the molecular simulation studies of adsorption on solid surfaces. First of all, various models of adsorbents used in different chromatographic modes are reviewed, including coarse-grained models and all-atom models, depending on the description precision required and the computational power provided. In the adsorbent models, the surface morphology is visualized using Monte Carlo simulation or molecular dynamics simulation. Then, studies on the adsorption and retention behaviors of small molecules by these models and methods are summarized. Finally, emphases are focused on the application of molecular simulation to protein adsorption, including protein–surface interaction, protein orientation and conformational transition on solid surfaces. In these studies, the effects of ligand parameters, including the ligand composition, ligand length, bonding density, ligand distribution have been examined. Meanwhile, chromatographic parameters, including the mobile phase composition and temperature, have also been investigated. Based on the successful applications reviewed herein, it is concluded that molecular simulation studies have contributed to the development of adsorption and chromatography in bioseparations. Moreover, it is suggested that molecular simulation combined with computational quantum chemistry and experiments would provide more comprehensive understanding of adsorption phenomena in the future.